CONTENTS
page
Editor’s
Page
American
Physiological
APS Membership
Future Meetings
Hypothalamus
Travel
i
.o..mm@..m..om.m.mm.mmmmmm.mmm.m.mm.mmm....e..m.
Status
l
Society
l
l
mm.....m..mmo................
301
mmmmmmmm.....mm..o.m..mmm..m.mm.o.e.
304
.*m...m........mm.......m.m.mm.om.......m..
in the Regulation of Energy and Water Balance
James A.F. Stevenson . . . . . . . . . . . . . . . . . . . 305
Grants for Tokyo Physiological
Regulation
of Pulmonary
AAAS Meeting
Biophysical
Ventilation
Society Meeting
Address..
... Fred S. Grodins
. Hermann
319
l
.
.
Rahn . . . . . . . . . . . . . . . . . . . 334
.m...mm.....mm..o.m.mom...m..me
342
.OOmeo*oom...*.momm..*.m...m...
343
. Robert E. Forster
News from Senior Members
.........
333
.m.m.m.m.m...m.m.mm.mm....mm.....
to the Far East
Tour..
. . . . . . . . . . . . . . . 318
333
AIBS . . . John R Pappenheimer
Councilman
Congress
..............................................
Past-President%
For Travelers
294
. ..m..m.m.......oo........o..o.
. ..m.....m00.....m.*m.m.347
350
EDITOR’S
PHYSIOLOGY
PAGE
TEACHERS
NEEDED
The Central Office of APS receives many inquiries for names of
physiologists
who may be interested in teaching positions.
Generally
the inquiring parties are referred to the Federation Placement Service
Office since The Physiologist is not designed to handle placement service activities.
However we are calling attention to two very earnest
appeals recently received mainly to emphasize the real need for more
trained personnel in our discipline.
The number of persons trained
in physiology each year has not kept pace with the steadily increasing
demand for trained personnel at all levels of experience.
The two cases in point at present are the University of California
at Davis and the Christian Medical College in India. The former can
be contacted by writing to Dr. F. W. Lorenz, Dept. of Animal Physiology; and the latter by writing to Dr. G. N. Constable at Ludhiana,
Punjab, India.
The recent emphasis on training programs sponsored by NIH should
eventually elevate this critical situation to some extent but professional
physiologists
must continue to recruit students at all levels of the educational ladder if we are to continue to have a discipline called physiology
and have teachers to train students for the future.
One means of recruiting
more young people for careers in physiology
is becoming effective through the Education Committee’s
program of
Visiting Scientists.
Many of the smaller schools requesting visiting
scientists have expressed the desire to have the scientist consult with
’ students about graduate training.
Several of the visiting scientists have
been able to successfully plead the case for physiology in these informal
talks and interviews,
in some cases picking up good applicants for graduate study in their own departments.
The Visiting Scientist program is continuing this year with more emphasis on personal conferences with students and teachers as well as
administrators
and less emphasis on formal seminars and lectures. Both
undergraduate
schools and visiting scientists are finding the program
highly rewarding.
Schools are permitted to select a visiting scientist
from a list of names and scientist interests.
This method necessarily
means that some scientists will not be called to make a visit whib
others will make several visits.
We hope scientists will continue to
make themselves available even though not called upon this year.
THE
AMERICAN
PHYSIOLOGICAL
Founded December
30, 1887; Incorporated
OFFICERS,
SOCIETY
June 2, 1923
1964-1965
President - John R. Pappenheimer,
Harvard Medical School, Boston,
Massachusetts
President-Elect
- John M. Brookhart,
University of Oregon School of
Medicine,
Portland,
Oregon
Past President - Hermann Rahn, University of New York at Buffalo,
Buffalo, New York
Council - H. Rahn(l965),
J. R. Pappenheimer
(1966), J. M. Brookhart
(19),
R. E. Forster (1965), L. D. Carlson (1966), K. S. Cole
(1967), J. D. Hardy (1968)
Executive Secretary-Treasurer
- R. G. Daggs, 9650 Wisconsin Avenue,
Washington,
D. C. 20014
STANDING
COMMITTEES
- R. W. Berliner
(1967), Chairman; C. N. Woolsey (1965),
Publications
R. E. Forster (1966)
Finance - L. N. Katz (1968), Chairman; H. S. Mayerson (1966), S. M.
my
(1967)
Membership
Advisory - L. D. Carlson (1965), Chairman; D. S. Farner
(1965), R. L. Riley (1965), C. P. Lyman (1965), H. D. Green (1966),
H. D. Patton (1967)
Education - R. B. Tschirgi (1967), Chairman; L. H. Marshall
(1965),
C. G. Wilber (1967), W. C. Randall (1967), D. K. Detweiler (1968);
Representatives
of Society of General Physiologists
- R. R. Ronkin
(1967), D. C. Tosteson (1968); Representatives
of Comparative
Physiology Division of the American Society of Zoologists - R. P.
Forster (1965), D. M. Maynard, Jr. (1965)
Use and Care of Animals - B. J. Cohen (1967), Chairman; E. Knobil
(1965), P. D. MacLean (1966)
Program Advisory - L. L. Langley (1965), Chairman;
R. M. Berne
(1966), W. L. Nastuk (1967)
Porter Fellowship
- J. K. Hampton (1967), Chairman; J. F. Perkins
(1965), D. W. Rennie (1966)
Senior Physiologists
- D. B. Dill (1965), Chairman; W. F. Hamilton
(1965), E. F. Adolph (1966), P. Bard (1966)
International
Physiology - M. B. Visscher (1965), H. S. Mayerson (1967),
E. M. Landis (1969)
REPRESENTATIVES
TO OTHER ORGANIZATIONS
American Association for the Advancement of Science - R. E. Smith
(1967), R. G. Daggs
American Institute of Biological
Sciences - J. R. Pappenheimer
(1966)
American Documentation
Institute - M. 0. Lee (1967)
National Research Council - Division of Medical Sciences - R. W. Gerard
(1967); Division of Biology and Agriculture
- A. F. Sellers (1967)
Council on Medical Education and Hospitals, A. M. A. - J. R. Brobeck(l967)
294
THE PHYSIOLOGIST
295
APS Members of the U. S. National Committee for IUPS - M. B. Visscher
(1965), H. S. Mayerson (1967), E. M. Landis (1969)
APS Members on the Federation Board - H. Rahn (1965), J. R. Pappenheimer (1966), J. M. Brookhart (1967)
Federation Advisory Committee - J. M. Brookhart
(1967)
Federation
Secretaries Committee - J. M. Brookhart
(1965), R.G. Daggs
A. C. Guyton (1967)
Federation Public Information
Committee
PUBLICATIONS
Publications
Committee - R. W. Berliner
1967), Chairman; C. N.
Woolsey (1965), R. E. Forster (1966)
Managing Editor - M. 0. Lee
Executive Editor - Sara F. Leslie
Chief Editor of Journal of Neurophysiology
- J. M. Brookhart
Editor of The Physiologist
- R. G. Daggs
Associate Editor of Physiological
Reviews - R. G. Daggs
Associate Editor of American Journal of Physiology and Journal of
Applied Physiology - R. L. Zwemer
EDITORIAL
BOARDS
American Journal of Physiology and Journal of Applied Physiology Section Editors - R. M. Berne, B. F. Hoffman (Circulation),
Jere
Mead (Respiration),
Jack Orloff (Renal and Electrolyte
Physiology),
Franklin Hollander (Gastrointestinal
Physiology),
Jane A. Russell,
R K. Meyer (Endocrinology
and Metabolism),
L. D. Carlson
(Environmental
Physiology),
Knut Schmidt-Nielsen
(Comparative
and General Physiology),
E. V. Evarts (Neurophysiology).
Editors - L. M. Beidler (1966), H. S. Belding (1966), W. J. Bowen
-(1966),
R W. Brauer (1966), W. A. Briscoe (1966), F. P. Brooks
(1965), V. B. Brooks (1965), F. P. Chinard (1965), J. A. Clements
(1966), P. F. Curran (1966), V. P. Dole (1966), A. B. DuBois (1965),
R. W. Eckstein (1966), L. E. Farhi (1967), R. P. Forster (1966),
W. H. Freygang, Jr. (1965), D. L. Dry (1967), W. F. Ganong (1966),
C. W. Gottschalk (1967), Eugene Grim (1965), Arthur Grollman (1966),
M. I. Grossman (1966), F. J. Haddy (1966), Allan Hemingway (1966),
R. H. Kellogg (1966), Ernst Knobil (1966), B. R. Landau (1965), F.N.
LeBaron (1965), Jean Mayer (1966), L. H. Peterson (1966), K. H.
Pribram (1965), E. P. Radford, Jr. (1967), J. W. Remington (1966),
Sid Robinson (1965), Aser Rothstein (1965), R. F. Rushmer (1966),
G. M. Schoepfle (1965), R. 0. Scow (1965), E. A. Sellers (1966),
J. W. Severinghaus (1966), J. T. Shepherd (1966), C. W. Sheppard
(1966), R. E. Smith (1965), S. M. Tenney (1965), Jay Tepperman
(1965), C. A. Terzuolo (1966), U. G. Trendelenburg
(1965), E. H.
Wood (1965), J. W. Woodbury (1966). Consultant Editors - A. F.
Cournand (1965), H. W. Davenport (1966), Hermann Rahn (1966),
E. E. Selkurt (1966).
Physiological
Reviews - J. R. Brobeck (1966), Chairman; V. E.
Amassian (1966), A. P. Fishman (1967), C. W. Gottschalk (1966),
W. L. Nastuk (1966), J. E. Rose (1965), R. C. Swan (1966), J. V.
Taggart (1966). Appointed from the Society of General Physiologists
-
296
THE PHYSIOLOGIST
T. H. Bullock (1966), I. M. Klotz (1965). Appointed from the American Society of Biological
Chemists - J. M. Buchanan (1967), A. E.
Wilhelmi (1966). Appointed from the &tierican
Institute of Nutrition Grace A. Goldsmith (1967). European Editorial
Committee - Eric
Neil, Chairman; N. Emmelin,
R B. Fischer, R A. Gregory, Y.
Laporte, G. Moruzzi.
Journal of Neurophysiology
- T. H. Bullock, R Granit, J. D. Green,
Elwood Henneman, B. Katz, S. IV. Kuffler, V. B. Mountcastle,
W. D. Neff, J. E. Rose.
Handbook of Physiology, Editorial
Committee - M. B. Visscher,
Chairman; A. B. Hastings (1966), H. Hahn (1967), J. R Pappenheimer
(1965).
Physiology for Physicians - E. A. Stead, Jr., Chairman; J. H. Comroe,
Jr., M. I. Grossman, I. M. London, I. H. Page, R. F. Pitts,
Stewart Wolf, J. B. Wyngaarden.
PAST OFFIC E RS
Presidents
- 1888 H. P. Bowditch, 1889-90 S. W. Mitchell,
1891-95
H. P. Bowditch, 1896-1904 R. H. Chittenden, 1905-10 W. H. Howell,
1911-13 S. J. Meltzer,
1914-16 W. B. Cannon, 1917-18 F. S. Lee,
1919-20 W. P. Lombard,
1921-22 J. J. MacLeod,
1923-25 A. J.
Carlson, 1926-29 J. Erlanger,
1930-32 W. J. Meek, 1933-34 A. B.
Luckhardt,
1935 C. W. Greene, 1936-37 F. C. Mann, 1938-39 W. E.
Garrey, 1938 W. T. Porter Honorary President,
1940-41 A.C. Ivy,
1942-45 P. Bard, 1946-47 W. 0. Fenn, 1948 M. B. Visscher,
1949
C. J. Wiggers, 1950 H. C. Bazett (April to July) D. B. Dill, 1951
R. W. Gerard, 1952 E. M. Landis. 1953 E. F. Adolph, 1954 H. E.
Essex, 1955 W. F. Hamilton,
1956 A. C. Burton, 1957 L. N. Katz,
1958 Hallowell Davis, 1959 R F. Pitts, 1960 J. H. Comroe, Jr.,
1961 H. W. Davenport,
1962 H. S. Mayerson,
1963 Hermann Rahn.
1893-94 W. P. Lombard,
18950
Secretaries
- 1888-92 H. N. Martin,
1903 F. S. Lee, 1904 W. T. Porter, 1905-07 L. B. Mendel, 1908-09
R. Hunt, 1910-14 A. J. Carlson, 1915-23 C. W. Greene, 1924-29
W. J. Meek, 1930 A. C. Redfield, 1931-32 A. B. Luckhardt,
193%
35 F. C. Mann, 1936-39 A. C. Ivy, 1940-41 P. Bard, 1942 C. J.
Wiggers, 1943-46 W. 0. Fenn, 1947 M. B. Visscher.
Treasurers
- 1888-92 H. N. Martin,
1893-94 W. P. Lombard,
1895-1903
F. S. Lee, 1904 W. T. Porter, 1905-12 W. B. Cannon, 1913-23 J.
Erlanger,
1924-26 C. K. Drinker,
1927-36 A. Forbes, 1937-40 W. 0.
Fenn, 1941 C. J. Wiggers, 1942-46 Hallowell Davis, 1947 D. B. Dill,
Executive Secretary-Treasurer
- 1948-56 M. 0. Lee, 1956 - R G.
wi3.w
297
THE PHYSIOLOGIST
CONSTITUTION
ASD BYLAWS
Adopted at the 1964 Spring Meeting
CONSTITCTIOS
ARTICLE
The name of this organization
SOCIETY.
I.
Name
is THE AMERICAN
ARTICLE
II.
PHYSIOLOGICAL
Purpose
The purpose of the Society is to promote
cal knowledge and its utilization.
the increase
of physiologi-
BYLAKS
(Amended
ARTICLE
April
I.
19611
Membership
Section 1. The Society shall consist of members, honorary members,
associate members, and sustaining associates.
Section 2. Members.
Any person who has conducted and published
meritorious
original research in physiolog
and, or biophysics and who
is a resident of North America shall be eligible for membership
in the
Society.
Section 3. Honorary Members.
Distiwished
scientists of any
country who have contributed to the advance of physiology shall be eligible for proposal as honorary members of the Society.
Section 4. Assoc iate Members.
-Advanced graduate students in
physiology at a predoctoral
level, teachers of physiology,
and investigators who have not yet had the opportunity or time to satisfy the requirements for full membership
shall be eligible for associate membership in the Society provided they are residents of North America.
Section 5. Sustaining Associates.
Individuals and organizations
who
have an interest in the advancement of biological
or biophysical investigation, may be invited by the President,
with the approval of Council,
to become sustaining associates.
ARTICLE
II.
Officers
Section 1. The management of the Society shall be vested in a
Council consisting of the President,
the President-Elect,
the PastPresident for the previous year, and four other members.
The terms
of the President and of the President-Elect
shall be one year. The
terms of the four additional Councilors
shall be four years each and
they shall not be eligible for immediate reelection except those who
have served for two years or less in filling interim vacancies.
A person may serve only one term as President,
except that if the PresidentElect becomes President after September 30 he shall continue as President for the year beginning the next July 1st.
298
THE PHYSIOLOGIST
Section 2. Nomination and election of a President-Elect
and Councilor(s) shall be by ballot at the Spring meeting of the Society. They shall
assume office on July 1 following their election.
Section 3. The President-Elect
shall serve as Vice-President
and
Secretary.
Should he have to function as President prematurely,
the
Council shall select from among its own members a Secretary.
Section 4. The Council shall be empowered to appoint and compensate an Executive Secretary-Treasurer
who shall assist it in carrying
on the functions of the Society, including the receipt and disbursement
of funds under the direction of the Council.
Section 5. The Council may fill any interim vacancies in its membership or vacancies on any Board or Committee of the Society, unless
otherwise provided.
ARTICLE
III.
Dues
Section 1. The annual assessment on members and on associate
members shall be determined by the Council and shall be due in advance on July 1.
Section 2. A member whose dues are two years in arrears shall
cease to be a member of the Society, unless after payment of his dues
in arrears and application to the Council, he shall be reinstated at the
next Spring meeting by special vote of the Council.
It shall be the duty
of the Secretary to notify the delinquent of his right to request reinstatement.
Section 3. A member who has retired from employment because of
illness or age may, upon application
to the Council, be relieved from
the payment of the annual member assessment.
ARTICLE
IV.
Meetings
Section 1. A meeting of the Society for transacting business, electing officers and members, presenting
communications,
and related
activities,
shall be held in the Spring of each year, with other member
Societies of the Federation of American Societies for Experimental
Biology, except that under exceptional circumstances
the Council may
cancel such a meeting.
Section 2. A Fall meeting of the Society shall be held at a time and
place determined by the Council, for presenting communications
and
for transacting business except the election of officers.
Section 3. Special meetings of the Society or of the Council may be
held at such times and places as the Council may determine.
Section 4. Regional meetings of the Society, for the purpose of presenting scientific communications,
may be authorized by the Council.
ARTICLE
V.
Publications
Section 1. The official organs of the Society shall be the American
Journal of Physiology, the Journal of Applied Physiology,
Physiological
Reviews and such other publications
as the Society may own.
Section 2. A Publications
Committee composed of three members
of the Society appointed by the Council shall be responsible for the manage
ment of all of the publications
of the Society; the Managing Editor, Exec-
THE PHYSIOLOGIST
299
utive Secretary and President of the Society shall be members ex-officio,
without vote. The Committee shall have the power to appoint a Managing
Editor and editorial boards for the Society’s publications.
The term of
each member of the Publications
Committee shall be three years; a member may not serve more than two consecutive terms.
The Council shall
designate the Chairman of the Committee who shall be an ex-officio member of the Council, without vote. The Committee shall present an annual
report on publications
and policies to the Council for approval and an
annual budget to the Finance Committee for its approval.
ARTICLE
VI.
Committees
and Representatives
Section 1. The Council may appoint such special and standing committees as it deems necessary or that are voted by the Society.
The Council may name members of the Society as representatives
to other organizations
whenever it deems such action desirable.
Section 2. A Finance Committee,
composed of three members of
the Society appointed by the Council, shall receive budget proposals
annually from the Committees,
the Council and the Executive Secretary
of the Society and shall determine the annual budget, reserve funds and
investments of the Society, subject to approval by the Council.
The capital fund of the present Board of Publication
Trustees (defined as the investments and unencumbered
funds of that Board as of
April 1, 1961) shall be a reserve fund for publications
and may be used
by the Publications
Committee to finance new or established publications without authorization
of the Finance Committee (though subject
to approval by Council).
The Finance Committee shall not approve the
expenditure of any of this capital fund for nonpublication
purposes without the consent of the Publications
Committee.
The Finance Committee
shall be responsible for the separate investment of the reserve fund for
publications;
any capital gains from such investment shall accrue to the
fund (capital losses will, however, reduce the value of it). Annual income from the investment of the fund may be used for any of the activities of the Society including publications.
The term of each member of the Finance Committee shall be three
years; a member may not serve more than two consecutive terms. The
Managing Editor, the President and the Executive Secretary shall be
ex-officio members, without vote. The Council shall designate the
Chairman of the Committee who shall be an ex-officio member of the
Council, without vote.
ARTICLE
VII.
Standing
Rules
Two members of the Society must join
1. Election to Membership.
in proposing a person for membership,
in writing and with a statement
of his qualifications.
The Council may, from the persons so proposed,
nominate candidates for election to membership.
Nominations shall
be presented at Spring and Fall meetings; a two-thirds
majority vote
of the members present and voting at the next following Fall or Spring
meeting shall be necessary for election.
If a Spring or Fall meeting of the Society is not held, the procedures
of nomination and/or election of new members may be effected by mail.
The names of the candidates nominated by the Council for member-
THE PHYSIOLOGIST
ship and statements of their qualifications
signed by their proposers
shal .l be available for inspection by membe rs during the Society meetings at which their election is consi dered.
2. Election to Honorary Membership.
The proposal of an honorary
member shall be made by two members of the Society to the Council in
w riting . The Council may, from the candidates so proposed, make nominations to the Society at a Spring meeting.
A two-thirds
majority vote
of the members present shall be necessary for election.
Honorary m.embe rs sha .ll have the privilege of attending bu siness
ses sions of the Society but shall have no vote. They shall pay no membership dues.
3. Election to Associate Membership.
Associate members shall
be proposed, nominated and elected in the same manner as full members.
Associate members shall have the privilege of attending business
sessions of the Society but shall have no vote. Associate members may
be nominated for full membership.
4. Presentation
of Papers.
At a Spring meeting of the Society, held
in conjunction with the Federation meetings, a member, retired member,
or honorary member must be one of the authors of each scientific paper
submitted to the Society for presentation.
Also a person’s name may
appear only once. An associate member or a non-member
may present,
orally one scientific paper only if a full member is a co-author.
At a
Fall meeting, a member, retired member, honorary member, or associate member may present orally not more than one paper.
Upon invitation by the Council, a member may contribute papers to
specially designated sessions of the Society without forfeit of his privilege of presenting a regular scientific communication.
5. There shall be a Committee on Membership
appointed by and
advisory to the Council.
6. There shall be a Program Advisory Committee appointed by the
Council.
ARTICLE
VIII.
General
Section 1. Amendments.
These Bylaws, except Article VlI, may
be amended at any Spring meeting of the Society by a three-fourths
majority vote of the members present.
The Standing Rules of Article VII may be amended by a majority
vote of the members present at either a Spring or Fall meeting of the
Society.
Section 2. Quorum.
At all business meetings of the Society fifty
members shall constitute a quorum.
Authority.
The rules contained in Roberts
Section 3. Parliamentary
Rules of Order shall govern the conduct of the business meetings of the
Society in all cases to which they are applicable and in which they are
not inconsistent with the Bylaws or special rules of order of the Society.
APS MEMBERSHIP
STATUS
OCTOBER
1964
Regular members
Associate members
Retired members
Honorary members
Total membership
SUSTAINING
2320
180
133
17
2650
ASSOCIATES
Abbott Laboratories
Ayerst Laboratories
Beckman Instruments,
Inc.
Burroughs Wellcome and Co.
CIBA Pharmaceutical
Products, Inc.
E thicon, Inc.
Gilford Instrument Laboratories,
Inc.
Gilson Medical Electronics
Grass Instrument Co.
Harvard Apparatus Co.
Hoffman-La
Roche, Inc.
Lakeside Laboratories
Eli Lilly and Co.
Merck Sharp and Dohme Research Laboratories
The Norwich Pharmacal Co.
Chas. Pfizer and Co., Inc.
Phipps and Bird, Inc.
Riker Laboratories,
Inc.
A. H. Robins Co., Inc.
Sherman Laboratories
Smith Kline and French Laboratories
The Squibb Institute for Medical Research
Tektronix,
Inc.
The Upjohn Co.
Warner-Lambert
Research Institute
Wyeth Laboratories
DECEASED
The following
MEMBERS
deaths were reported
since the 1964 Spring meeting.
R. H. Beutner (R) - April 15, 1964
Paul M. Harmon (R) - July 16, 1964
E. A. Hewitt (R) - December 29, 1963
Henry A. Imus - May 18, 1964
Yale J. Katz - December 6, 1963
Simon A. Komarov - March 29, 1964
George Misrahy - March 7, 1964
W. J. Osterhout (R) - April 9, 1964
Charles M. Pomerat - June 17, 1964
Julian Tobias - April 12, 1964
Charles I. Wright (R) - April 16, 1964
301
THE PHYSIOLOGIST
302
NEWLY
ELECTED
MEMBERS
The following,
nominated by the Counci ’ 19 were elected to membe rship in the American Physiological
Society at the Fall meeting, 1964
FULL
MEMBERS
ADAMS, Thomas: Asst. Prof. Res. Physiol.,
Univ. Oklahoma Med. Sch.
AKERS, Thomas K. : Asst. Prof. Pharmacol, , Stritch Med. Sch., Loyola
ANGELONE,
Luis: Assoc. Prof. Physiol. , Washington Univ. Dent. Sch.
ARMALY,
Mansour F. : Assoc. Prof. Ophthalmol.,
State Univ. Iowa
ASCANIO, Guido: Asst. Prof. Physiol.,
Temple Univ. Med. Sch.
BENTIVOGLIO,
Lamberto G. : Cardiac Cath., Albert Einstein Med. Ctr.
BICKFORD, Arthur F. : Assoc. Staff, Cardiovascular
Res. Inst., Univ.
California
BIRD, John W. C. : Asst. Prof. Physiol.,
Rutgers Univ.
BORLE, Andre B. : Asst. Prof. Physiol.,
Univ. of Pittsburgh
BOUHUYS, Arend: Asst. Prof. Physiol. & Med., Emory Univ.
BRAY, George A. : Asst. Physician,
New England Center Hosp.
Colorado State Univ.
BREDECK, Henry E . : Assoc. Prof. Physiol.,
BUNNELL,
Ivan L. : Assoc. Prof. Med., State Univ. New York, Buffalo
CARDUS, David: Asst. Prof. Physiol. & Rehab., Baylor Univ.
CASSIN, Sidney: Asst. Prof. Physiol.,
Univ. of Florida
CELANDER,
David R : Prof., Chmn. Biochem.,
Coll. Osteopathic Med.
CHIDSEY, Charles A. : Sr. Investigator,
Cardiology Br., NH1
CLAPP, James R : Assoc. Med., Duke Univ. Med. Ctr.
COLLINS, William F., Jr. : Prof. Neurol. Surg., Med. Coll. Virginia
COOPER, Bernard A. : Asst. Prof. Med. & Clin. Med., McGill Univ.
DALY, Walter J. : Asst. Prof. Med., Indiana Univ. Sch. Med.
DANFORTH,
William F. : Prof. Physiol.,
Illinois Inst. Technology
DaVANZO, John P. : Lect. Pharmacol.,
Med. Coll. of Virginia
DAVIS, Robert P. : Asst. Prof. Med., Albert Einstein Coll. Med.
DAVIDSON, Julian M. : Asst. Prof. Physiol.,
Stanford Univ.
DOWNIE, Harry G. : Prof, , Head Physiol. Sci. , Ontario Vet. Coll.
DUTTON,
Robert E. : Instr., EnvironMed.,
Johns Hopkins Univ.
EBLE, John N. : Sr. Res. Pharmacologist,
Pitman-Moore
Co.,
Indianapolis
EMERSON, Geraldine M. : In&r. Biochem.,
Univ. of Alabama Med. Ctr.
ESSIG, Alvin: Instr. Med., Harvard Med. Sch.
FLAMBOE,
Eugene E. : Assoc. Prof. Physiol.,
Colorado State Univ.
FRAYSER, Katherine R : Asst. Prof. Med., Physiol.,
Indiana Univ.
GAENSLER,
Edward A. : Res. Prof. Surg. , Boston Univ. Sch. Med.
GILLENWATER,
Jay Y. : Res. Fell. Renal & CV, Bockus Res. Inst.
GINSBURG, Jack M. : Asst. Prof. Physiol.,
Univ. of Rochester
GOLD, Ernest M, : Assoc. Prof, Med., UCLA
GOLDSMITH,
Dale P. J. : Instr. Physiol.,
Univ. of Rochester
GORDON, Helmut A. : Prof. Pharmacol.,
Univ. of Kentucky Med. Coll.
GORSKI, Jack: Asst. Prof. Physiol.,
Univ. of Illinois
GRAY, Seymour J. : Assoc. Clin. Prof. Med., Harvard Med. Sch.
GROLLMAN,
Arthur P. : Assoc. in Med., Molecular
Biol., Albert
Einstein Coll. Med.
GROSS, Nathan B. : Prof. Physiol. , Psychol.,
Univ. of Michigan
GUNTHEROTH,
Warren G. : Assoc. Prof. Pediat., Univ. of Washington
THE PHYSIOLOGIST
303
HAFT, David E. : Assoc. Prof. Med., New York Med. Coll.
HERD, James A. : In&r. Physiol.,
Harvard Med. Sch.
HILLS, Arthur G. : Prof. Med., Chmn. Sect. Metabol.,
Univ. of Miami
IBER, Frank L. : Asst. Prof. Med., Johns Hopkins Univ. Sch. Med.
ISAACSON, Allen: Asst. Mem., Physiol. Div., Inst. Muscle Disease
JOHNSON, Donald C. : Asst. Prof. Gynecol. & Obstet., Kansas Univ.
JOHNSON, Edward A. : Assoc. Prof. Physiol.,
Duke Univ. Med. Ctr.
JONES, Richard D. : Assoc. in Res., St. Luke’s Hosp., Cleveland
KALDOR, George J. : Res. Assoc., Phys. Chem., Isaac Albert F&s. Inst.
KAPPAS, Attallah: Assoc. Prof. Med., Univ. of Chicago
KATZ, Joseph: Sr. F&s. Assoc., Cedars of Lebanon Hosp.
KAUFMAN,
William C. : Res. Biologist,
Aerospace Med. F&s. Labs.
KITTLE,
C. Frederick:
Assoc. Prof. Surg., Univ. of Kansas
KRIEGER, Dorothy T. : F&s. Asst. Med. 9 Mt. Sinai Hosp., New York
KRUM, Alvin A. : Asst. Prof. Physiol.,
Univ. of Arkansas
LANDAU, Bernard R : Assoc. Prof. Med., Western Reserve Univ.
LAUBER, Jean K. : Asst. Prof. Animal Sci., Washington State Univ.
LAYNE, Donald S. : Staff Scientist, Worcester
Fndn. Exptl. Biol.
LEE, James B. : Dir. Metabol. F&s., St. Vincent Hosp., Worcester, Mass.
LENDE, Richard A. : Asst. Prof. Neurosurg.,
Univ. Colorado Med. Ctr.
NASA Ames Res. Ctr.
LEON, Henry A. : Independent Res., Res. Scientist,
LILLEHEI,
Hichard C. : Assoc. Prof. Surg., Univ. of Minnesota
LINDSLEY,
David F. : Asst. Prof. Physiol.,
Stanford Univ.
LINKENHEIMER,
Wayne H. : Group Leader, Physiol., Pharmacol.,
Am.
Cyanamid Co,
LODGE, James R : Assoc, Prof. Physiol.,
Dairy Sci., Univ, Illinois
LUHBY, A. Leonard: Assoc. Prof. Pediat., New York Med. Coll.
MALLOV,
Samuel: Assoc. Prof. Pharmacol.,
State Univ. New York,
Syracuse
MCKENZIE, John M, : Asst. Prof. Med. & Clin. Med., McGill Univ.
MELI, Albert0 L. G. : Sr. Ijes. Assoc., Warner-Lambert
Res. Inst.
MOSER Kenneth M, : Asst. Prof. Med., Georgetown Univ. Hosp.
MOSES, Arnold M. : Staff Physician, In&r, Med., State Univ. New York,
Syracuse
MOSS, Arthur J. : Res. Fell. & Ihstr. Med., Univ. Rochester Med. Ctr.
MUNCK, Allan U, : Assoc. Prof. Physiol.,
Dartmouth Med. Sch.
NELSON, Phillip G. : Physiol.,
Neurophysiol.,
NIH
NIKITOVITCH-WINE
R Miroslava
B. : Asst, Prof. Anat., Univ. Kentucky
Univ. of Miami
NUNN, Arthur S., Jr. : Asst. Prof. Physiol.,
O’BRIEN, George S. : Res. Assoc., CV Res. Lab., Univ. of Wisconsin
OPPENHEIMER
Jack H. : Endocrine Res. Lab., Montefiore Hosp.
PINNEO, Lawrence R : Res. Assoc., Head Lab. Neurophysiol.,
Tulane
Univ.
PLAGER, John E. : Res. Dir., Med. Fndn, of Buffalo
HANCK, James B., Jr., Asst. Prof, Physiol.,
Univ. of Michigan
HEED, Donal J. : Res. Instr.,
Pharmacol.,
Univ. of Utah
RICHARDS, A. Glenn: Prof. Entomol.,
Fisheries
& Wildlife,
Univ. of
Minnesota
ROBINSON, Roscoe R : Asst. Prof, Med., Duke Univ. Med. Ctr.
SALZMAN,
Edwin W. : Instr. Surg., Harvard Univ. Med. Sch.
SCHINDLER
William J. : Asst, Prof. Physiol.,
Baylor Univ.
SCHLAG, John D. A. : Asst. Prof, in Residence, Anat. & Brain F&s.,
UCLA
304
THE PHYSIOLOGIST
SCHONBAUM,
Eduard: Assoc. Prof. Pharmacol.,
Univ. of Toronto
SCHREINER, Bernard F., Jr. : Asst. Prof. Med., Univ. of Rochester
SIEGEL, John H. : Clin. In&r., Teach. Assoc. Surg., Univ. of Michigan
SOMJEN, George G. : Asst. Prof. Physiol.,
Duke Univ. Med. Ctr.
STEINER, Sheldon H. : Asst. Prof. Med., Indiana Univ.
SUTIN, Jerome: Assoc. Prof. Anat., Yale Univ.
CV Res. Inst., Univ. California
TAYLOR,
Fletcher B. : Res. Physician,
ULVEDAL,
Frode: Res. Physiol.,
USAF Sch. Aerospace Med., Brooks
AFB
WALDMANN,
Thomas A. : Sr. Investigator,
Metabol. Serv., NIH
WEISBERG, Howard: Res. Assoc., CV Inst. Michael Reese Hasp,
Metabol. Serv., MH
WEISSMAN, Sherman M. : Sr. Investigator,
WELTMAN,
A. Stanley: Assoc. Prof. Pharmacol.
& Res., Brooklyn
Coll, Pharmacy
WILLIS, William D., Jr. : Asst. Prof. Anat., Univ. of Texas
WINDHAGER,
Erich E. : Asst. Prof. Physiol.,
Cornell Univ. Med. Coll.
WINKERT, John W. : Instr. Physiol.,
Pharmacol.,
New York Med. Coll.
ASSOCIATE
MEMBERS
BIGNALL,
Keith E. : Postdoctoral
Fellow, Univ. of Paris
CARRIER, Oliver, Jr. : Res. Fell. Physiol.,
Univ. of Mississippi
CHASE, Michael H. : Doctoral Candidate Physiol, , UCLA
CROPP, Gerd J. A. : Grad. Student, Univ. of Western Ontario
GOETZ, Kenneth L. : In&r. Physiol,,
Univ. of Kansas
GORDON, Albert McC. : Instr. Physiol. & Biophys.,
Univ. Washington
HANSON, Kenneth M. : Res. Assoc. Physiol.,
Indiana Univ. Med. Ctr.
HOULIHAN,
Rodney T. : Asst. Prof. Zool, , Pennsylvania State Univ.
MILLER,
L. Keith: Sr. Res. Asst., Zoophysiol.,
Univ. of Alaska
ROBERTSON,
Patricia A. : Grad. Student, Loyola Univ., Chicago
ROBERTSON, William G, : Aviation Physiol.,
USAF Sch. Aerospace Med.
Fellow, Univ. of Mississippi
SMITH, Elvin E. : Postdoctoral
WEBER, William A. : Assoc. Prof., Head Dept. Biol. Sci., Quincy Coll.
FUTURE
1965
1965
1965
19 66
1966
1967
1967
1968
1968
1968
MEETINGS
Spring - Atlantic City, N. J., April 9-14
Fall - Univ. of California at Los Angeles, August 24-28
KJPS - Tokyo, Japan, September l-9
Spring - Atlantic City, N. J., April 11-16
Fall - Baylor Univ., Houston, Texas
Spring - Chicago, Ill., April 16-21
Fall - Howard Univ., Washington,
D. C.
Spring - New York City, April 7-12
Fall - Will be cancelled because of Congress in Washington
IUPS - Washington, D. C., August 25-30
THE
HYPOTHALAMUS
IN THE REGULATION
OF ENERGY
AND WATER
BALANCE*
JAMES
A. F. STEVENSON
Since the demonstration
some 20 years ago that the obesity associated
with pathological
and experimental
lesions in the region of the hypothalamus and pituitary is primarily
due to overeating or hyperphagia (19),
we have learned a great deal about the regulation of food and water intake
by the central nervous system. As our knowledge increases,
our explanations may become more precise but they also become more complex.
In the middle of the last decade the matter seemed simple.
There was a
“feeding centre” in the lateral, and a “satiety centre” in the ventromedial
hypothalamus (4, 49). The site of regulation of water intake was not quite
so clear; in the rat it appeared to be in the lateral hypothalamus (32,55,83)
but in the goat (11) and dog (43) more anterior and medial.
Subsequent
investigations
have revealed that the neurophysiological
systems for the
regulation of food and water intake are very complex, being evident as
well in other parts of the hypothalamus and, indeed, in other parts of
the ne rvous system.
Sac tion
inhib.
STIMULATION
FWO
WATER
INTAKE
INTAKE
Y - MOTIVATION
or FEEDING
01 DRINKING
A- ADRENALINE
ABLATION
INC.
DEC.
INC.
A
V
Av
DEC.
8
AC - ACETYLCHOCINE
Fp - FECUNG
IN PROGRESS
Fig. 1. Diagramatic
outline of regions in nervous sys tern that abl .ation,
or stimulation,
has shown to influence food and water intake. The broke n
line encloses the hypothalami .c region; F. L. refers to frontal lobe, TS
to tractus sol itarius, &W to region where ablation impairs food and water
intake only in response to variations in environmental
temperature.
*Based on presentation
at Symposium presented at the Autumn
Meeting of the American Physiological
Society, University of Miami,
Coral Gables, Florida,
August 30, 1963.
305
306
THE
PHYSIOLOGIST
Fig. 1 provides a diagramatic
representation
of some of the regions
that influence food and water intake significantly
according to the results
of various ablation and stimulation
experiments.
In the hypothalamus,
ablation in the ventromedial
region produces hyperphagia and obesity
(19,20).
If the lesions are anterior and ventral, hyperdipsia (44), secondary to diabetes insipidus from destruction
of the supraopticohypophyseal
tract, may also occur; but, if the lesions are on the lateral aspect, a
relative hypodipsia and chronic dehydration are associated with the hyperphagia (83). Slightly more laterally,
an absolute hypodipsia without hyperphagia is encountered following ablation (656).
Stimulation in the ventromedial region tends to decrease food intake (7, 57,64, 78,101) while anesthesia of this region prevents the inhibition of feeding by gastric distension
(40). Ablation at certain points in the posterior
hypothalamus causes
significant but less profound changes in food intake (84).
Ablation in the lateral hypothalamus results in adipsia in the rat (55).
The aphagia that also occurs following these lesions led to this region
being considered a “feeding centre” (4, 5). The argument as to whether
or not this aphagia is a truly permanent effect and is due to a regulatory
(27) or to a motor deficit (15) remains open. Although the spontaneous
intake of water may be regained following such lesions, it is now dependent upon the intake of food - the animal apparently learns to eat water;
spontaneous regulation of intake of water per se in response to natural
exigencies is not recovered (27,28).
The-ion
of feeding and drinking by stimulation
in the lateral hypothalamus (24,32,35,39,47,
79,95)
confirms that important systems for the regulation of food and water intake lie here. The observations of Morgane (58) indicate the complex
nature of these systems which apparently involve facilatatory
or motivational elements.
As mentioned,
stimulation
more anteriorly
and medially in the hypothalamus of the goat induces drinking,
and ablation in this region in the
dog causes an adipsia.
This may be a true species difference from the
rat, but, since Andersson has shown that cooling the preoptic hypothalamus of the goat evokes feeding and inhibits drinking, while warming
has the opposite effects (10,12), one may also postulate, as suggested
earlier (85), that this anteromedial
site of stimulation
of drinking in the
goat is part of an important pathway from the thermoregulatory
systems
in the preoptic area to a fundamental hydroregulatory
system in the
lateral hypothalamus.
The evidence that lesions in this anterior region
disrupt adequate regulation of food and water intakes in response to
variations in environmental
temperature
supports this view (38, 85, 87).
Thermoregulation
requires adequate regulation of water and food intakes;
in some species, it may exert the paramount control.
Recent observations
suggest that osmoreceptors
that facilitate or
inhibit water drinking,
as well as renal water loss, may be situated in
the anterior hypothalamus (80) and there is evidence that osmosensitive
elements occur in other parts of the nervous system (92). Water intake
is also influenced by other regions of the hypothalamus; both stimulation
and destruction
in the premammillary
area may cause some increase of
water intake (48, 70, 72, 76, 84).
THE PHYSIOLOGIST
Ablations in several other regions of the brain have not produced
marked effects on drinking or feeding (8,9) with the exception of those
in the amygdala (31,46,59, 60, 61,62,100) in the brain stem (1, 7582)
and in the dorsal longitudinal
fasciculus (22), which lead to some degree
of hyperphagia,
and ablation in the caudate nucleus, which may cause
hypophagia or aphagia (8,9,85).
Excepting the amygdala, it would perhaps be permissible,
until shown otherwise,
to consider these effects
as due to interruption
of sensory and motor systems.
The inhibition
of
feeding that has been obtained from stimulation
of the caudate (63) could
be due to activation of an afferent inhibitory system for which evidence
has currently been produced (‘74). Although it is generally agreed that
ablation of the amygdala results in a hyperphagia,
the effects of stimulation here on food and water intake vary with the site and type of stimulation as well as with the state of the animal (36,68,97).
It is interesting
that the exhibition of adrenaline
in the cortical nucleus of the amygdala
enhances feeding and depresses drinking,
but only if these activities are
already in progress; acetylcholine
has opposite effects (36). These same
agents have a more powerful influence in the lateral hypothalamus where
adrenaline will evoke feeding and acetylcholine
drinking,
even in the
satiated animal (35) - conversely these activities are inhibited by the
local application of the appropriate
blocking agents (37). These observations have led to the suggestion that the feeding systems may be adrenergic and the drinking systems cholinergic.
Section of the frontal lobes has been reported to increase food intake
in both man and animal but in many instances this appears to have been
secondary to a change in mood or to an increase in physical activity.
However, there may well be inhibitory mechanisms to feeding and drinking in the frontal lobes, for section of these lobes removes the inhibitory
effect of amphetamine
on water and food intake (13). At the other end of
the brain, stimulation
in the region of the dorsal motor nucleus of the
vagus has elicited feeding, even of contaminated food (47).
At this point it seems reasonable to postulate that the hypothalamus
contains the fundamental systems for regulating food and water intake,
particularly
those related to other vital aspects of homeostasis such as
therm0 - and osmo- regulation.
There is also evidence that chemoregulatory systems to adjust food intake to the needs for carbohydrate and
fat may be located in the hypothalamus.
The fundamental hypothalamic
systems are affected not only by local events and peripheral
afferent
systems but also by higher systems, particularly
in the limbic or visceral brain, with which the hypothalamus has many association pathways.
Stimulation along several of these pathways has been found to influence
immediate feeding and drinking behavior (29, 67, 69). The circuitry
of
the neurophysiological
and neuroanatomical
systems for these regulations
appears to be very complex, but this is not surprising
when we consider
all the factors, with their various priorities,
that affect food and water
intake in animal and man (2).
Various attempts have been made to construct integrated hypotheses
to describe at least the major or fundamental regulatory mechanisms
for food and water intake (3,14,16,17,33,45,50,
51,52, 73,85,87,96).
Those for feeding which have received emphasis recently are listed in
308
THE PHYSIOLOGIST
Table I. So far, none alone seems adequate to explain
regulation of food intake.
Table I.
Current
Hypotheses
Gastrointestinal
of the Regulation
-A.
B.
C.
of Food Intake.
Oral-Pharyngeal
Distension
Effects on osmolarity
Thermostatic
-Peripheral
Glucostatic
-Specific
Lipostatic
-Concentration
Liponeurostatic
-Innervation
Amino Acid Pattern
-Pattern
Combinations
all facets of the
and central
receptors
of ECF
heat monitors
for glucose
of circulating
metabolite
of fat tissue
of amino acids in ECF
of above
The inhibitory effect of gastric distension is well accepted. It probable serves as both a safety signal and as a conditioned or learnt cue.
Relearning,
or adjustment to changes, ‘of this cue probably occur when
the caloric density of the diet is varied.
Afferent pathways from the
stomach travelling via the vagus (41,42,53,65,91)
or sympathetic nerves
(34,42,94) apparently pass through the ventromedial
hypothalamus to
reach the lateral systems (40); they may also reach the caudate (74).
This gastric mechanism,
however, must depend on some more fundamental one, in relation to which it is set or appreciated,
e. g. when the
caloric density of the diet is varied.
It has long been held that hunger is inversely related to the concentration of blood glucose and Mayer and his colleagues (50,51) have contributed much to the elucidation of how food intake may be regulated in
relation to carbohydrate metabolism.
They have concluded that it is
the cells’ need for glucose, reflected in the rate of uptake and thus in the
A-V difference,
that signals hunger and, in turn, satiety through specific
hypothalamic neurones (49). There is no doubt that hunger and hypoglycemia frequently occur together and that insulin produces hypoglycemia
and increases the food intake (50). There are however, many clinical
and experimental
situations in which the control of food intake shows no
obvious correlation
with any parameter of the blood glucose (e. g. 30,66).
Further,
rats regulate their food intake well over long periods on a carbohydrate-free
diet (fig. 2) and show no, or little, difference at a twohour meal in the rate or amount of intake of such diet compared to those
on a normal high carbohydrate
diet (fig. 3). Indeed, the rate and amount
of food intake at a three-hour
meal are almost identical whether the diet
THE PHYSIOLOGIST
309
be high (60-70s calories) in carbohydrate
or fat (fig. 4). It is interesting
that a low protein diet (5.9% of calories),
which depresses food intake
in man and animal, causes an early satiety as far as the consummatory
response is concerned if the animals are accustomed to this particular
diet. On the other hand, the hypothalamic hyperphagic rat does not
show a hyperphagia on a high protein diet (89) although it can and does
increase its intake of this diet when exposed to a cold environment,
as
does the intact animal (85). This inhibitory effect of a protein diet might
be attributed to the high SDA of protein, but why then is there also a decreased intake on a low protein diet?
HCD
1
NCD
s
z?
0
I
3
5
7
TIME
- weeks
I
3
5
7
Fig. 2. Average daily food intakes each week over an eight- leek period
in which one group of six rats was fed a high carbohydrate
diet and a
second group of six was fed a non-carbohydrate
diet, ad libitum.
The effects of environmental
temperature
on food and water intakes
are well known (16) and we have recently found that a high or low environmental
temperature
even if only for a period of a brief meal will
inversely affect the food intake at that meal. These environmental
or
peripheral
effects are paralleled
by similar effects of local temperature
changes in the preoptic hypothalamus which have been already discussed.
Present evidence suggests that it is an integration
of information
from
peripheral,
as well as central thermoreceptors
that mediates the final
influence of temperature
on food and water intakes in the healthy animal.
Such an integration
could provide a measure of the body’s insulation, i. e.
of the fat stores - a thermolipostatic
mechanism.
The decrease which
some agents cause in food intake has been attributed to their hyperglycemic action, e.g. glucagon (23) and adrenaline
(71,81), but these particular agents also cause an increase in heat production;
insulin, which
causes an increase in food intake, tends to lower the core and skin temperature as well as the blood sugar (86). Which, if either, of these
effects is the critical signal?
The attempt to analyze the signals that affect the hypothalamic
and
associated regulating systems is not easy. With the present hypotheses,
how is one to explain the observation in man and in the rat that irregular
bouts of exercise often decrease the food intake on the day of exercise
with a compensatory increase one or two days later?
We have recently
observed that insulin can offset this decrease after exercise (86).
THE PHYSIOLOGIST
310
PERlOOlC
30
60
I20
TIME - mh
30
60
Ii
120.
10.
c,
io
-I
IICD
“**--*’ 0
N cD
SO
TIME - mln
1
0S.E.Y.
I
Ii0
Fig. 3. Periodic and cumulative food intakes of rats for the first twohour period of ad libitum feeding following a 24-hour fast. The rats had
previously been accustomed to the diet on which they were tested. Below are shown the concurrent changes in blood glucose.
The hyperphagia that follows ablation of the ventromedial
region
has often been attributed to the destruction of a satiety center and while
there is much evidence that some inhibitory pathways which subserve
satiety are destroyed by this lesion, not all inhibitory
systems for feeding run through this region.
The sensitivity of hypothalamic hyperphagic
rats to aversive qualities of the diet or of the feeding situation has been
demonstrated
(54,93).
Anorexigenic
agents such as amphetamine and
phenmetrazine
cause an aphagia in hyperphagic obese rats which may
persist for some time after the drug is stopped (18,25,89,90).
It is
possible that the inhibition they produce originates in the frontal lobes
311
THE PHYSIOLOGIST
16
HCD
I2
I a PERIODIC
0 CUMULATIVE
6 RATS/GROUP
NFD
1
LPD
TIME - hrr
l/2
I”2
3--6
-
Fig. 4. Periodic and cumulative food intakes for rats on a six-hour
feeding regime eating high carbohydrate
(HCD), non-carbohydrate
(high fat, NCD), low fat (NFD) and low protein (LPD) diets which were
all isocaloric.
(13); in any case, the inhibitory system involved is not destroyed by
ventromedial
ablation.
We have recently investigated the effects of
another agent in these hyperphagic animals.
Chalmers and his colleagues (21) several years ago reported the extraction of a substance
from urine of fasting human beings that was similar in its biological
activity to the urinary extract from fasting rabbits which Weil and
Stetten (98) had found would mobilize fat to the liver.
In the intact
mouse, the human extract caused transient hypoglycemia,
ketonemia,
hyperlipemia,
and increased mobilization
and catabolism of fat, with
depletion of fat stores leading to a loss of body weight and, according
to these investigators,
it did this withour causing any decrease in food
intake. Following the extraction procedure of Chalmers and his colleagues, we have obtained a substance from the urine of fasting rats
which appears to be similar,
on paper chromatography,
in amino acid
composition and to have the same biological properties
as the human
extract (88). We have found, however, that, when this material was
injected into rats, the reduction in body weight was related to a decrease
in food intake, which is easier to measure in the rat than in the mouse
(fig. 5). Like the amphetamines,
this substance has a much more pro-
312
THE PHYSIOLOGIST
found effect on food intake in the hypothalamic hyperphagic than in the
normal animal.
This substance causes a marked increase in the blood
FFA in vivo and in the release of FFA from the rat’s epididymal fat
pad in vitro.
If anything, it reduces oxygen consumption.
Upon first
examination,
these particular
observations would fit the lipostatic hypothesis for the control of food intake much more easily than the glucoor thermostatic
hypotheses.
a
IO- /
INJECTION. (Smg f M S /RAT)
WZ
0’
ZE
a ooMl
5
c
*.:
‘.
3
G
‘.
*.
-IO-
3
*.
: *.
*.*-..
.*.*
.-.*
*...*.
‘...,...-
.a.*
.’
.- .*
l ..*
/
.*.-*.*
. ...*
a
. . . . . .. . . -=
l.
.CONTROL
(3)
H*OBESE
(33
-i
0
2
4
6
6
IO
-2
0
2
4
6
6
IO
TIME
DAYS
Fig. 5. The effect of one injection (s.c.) of FMS (5mg/rat) on the body
weight, food intake and water intake of control and hypothalamic obese
female rats. At the time of injection,
the control rats weighed an average of 297 gm. and the hypothalamic
rats weighed an average of 607
gm*
Further problems arise in explaining the long-term
factors that
affect food intake. When rats that have had their food intake restricted
for a sufficient period during growth are later given food ad libitum,
they gain some of the weight they have missed, by over-eating for a
short period but then they stabilize at a smaller body size and food intake than the controls that have always eaten ad libitum.
The food intake of these animals can be markedly increased by exposure to cold
or by administration
of insulin but, upon removal of such stimuli.
it
falls back to its former lower level and these animals do not gain to their
313
THE PHYSIOLOGIST
normal potential size (86). With insulin, they can be brought to the control weight but this gain is lost when the insulin is stopped (fig. 6). These
animals appear to have accepted a new metabolic size, imposed by the
previous restriction,
and now regulate their food intake in relation to
this. What mechanism can explain this regulation?
Perhaps a thermolipostatic hypothesis may serve, but this is not yet demonstrated.
0
I
1
40
31-40
I
50
41-50
1
60
51-60
61-70
AGE
I
70
80
71-80
- DAYS
1
90
81-90
91-100
I
100
I
120
II0
101-112
113-122
1
I30
123-132
1
140
133-142
.
tso
143-l%
Fig. 6. Body weight curves and average daily food intakes for weanling
rats restricted at 30 days of age to a one-hour feeding period per day.
At 70 days of age, the rats were allowed to feed ad libitum until 100
days of age at which time the previously restricted
group was divided ten rats received daily injections of protamine zinc insulin, five received daily injections of normal saline, and five were placed in an
After 12 days of
environment of 5oC along with five of the controls.
this treatment all animals were returned to ad libitum feeding at 240C
until the end of the experiment
at 150 days of age.
None of the current single-factor
hypotheses for the regulation of
food intake appears to be adequate alone to explain the apparent variety
of controls of food intake (fig. 7). But is this surprising
in view of what
we now know, particularly
from the work of Adolph (2), about the priorities
Several systems for even the fundaof regulation in the whole animal?
mental control of food intake seem appropriate
when one considers the
several vital aspects of homeostasis which it affects.
The situation with regard to the control of water intake is similar.
There is good evidence that osmometric
(99), volumetric
(77) and
thermometric
(10) mechanisms are fundamental in this control. Again,
314
THE PHYSIOLOGIST
Fig. ‘7. On the left, a diagramatic
working hypothesis of some of the
fundamental clues or signals that influence water and food intake.
Several of these, such as the temperature,
have peripheral
as well as
central sensors; for others there may be only peripheral
or central
sensors.
Many of the factors in the external environment and the emotional or motivational
state of the animal are sensed and integrated
through higher systems, particularly
the visceral brain-limbic
system.
There are many association pathways available for transmission
of information between the cortical,
hypothalamic
and lower systems.
The figure on the right demonstrates
some of the postulated systems
within the hypothalamus involved in the regulation of food and water
intake. The grid refers to sterotaxic coordinates
1 mm. apart.
1. Inhibitory and/or facilitatory
pathways from the anterior thermoregulatory systems which are activated by thermal stimuli (Andersson)
and interfered with by lesions in the anterior (Hamilton and Brobeck;
Stevenson) and in the anterior ventromedial
(Montemurro
and Stevenson)
hypothalamus.
2. A pathway inhibitory to water intake from the supraoptic region, perhaps from osmoreceptors
as suggested by the observation of Smith and
McCann.
3. A possible pathway from chemoreceptors
in the ventromedial
region.
4. Inhibitory pathways from the gastrointestinal
tract, subserving gastric
distension,
swallowing,
etc. , and, perhaps, peripheral
chemoreceptors.
5. and 6. Motivational
systems in the median forebrain bundle (Morgane)
and, by an analogy, other association pathways.
7. Some facilitatory
pathways for feeding apparently pass through the VM
region as suggested by the observations of Miller et al. and of Teitelbaum.
These all appear to focus on the fundamental systems for the execution of
drinking and feeding behavior ti the lateral-far
lateral hypothalamus.
THE PHYSIOLOGIST
315
several mechanisms would permit the interplay of priorities
in the
overall regulation.
As with food intake the gastrointestinal
tract probably provides important immediate cues, which may serve as conditioned stimuli.
Dryness of the mouth enhances thirst subjectively,
the act
of swallowing
and gastric distension provide immediate measure of intake (26,33).
The present discussion
controls of food and water
thalamus.
Superimposed
the immediate exigencies
bases of these secondary
It is apparent, however,
both the fundamental and
has dealt only with some of the fundamental
intake which appear to be focused in the hypoon these are the influences of emotion and of
of the environment.
The neurophysiological
influences are now beginning to be revealed.
that we still have a great deal to learn about
ancillary controls of these intakes.
REFERENCES
1. Adametz, J., and J. L. O’Leary. Neurology
9:636-642, 1959.
2. Adolph, E. F. Physiological
Regulations.
Lancaster,
Pa. : Jaques
Cattell Press, 1943, 502~.
3. Anand, B. K. Physiol. Rev. 41:677-708,
1961.
4. Anand, B. K., and, J. R. Brobeck. Proc. Sot. Exptl. Biol. Med.
77: 323-324, 1951.
5. Anand, B. K. , and J. R. Brobeck. Yale J. Biol. Med. 24: 123-l 40,
1951.
6. Anand, B. K., and S. Dua. Indian J. Med. Res. 46: 426-430, 1958.
7. Anand, B. K., and S. Dua. Indian J. Med. Res. 43: 113-122, 1955.
8. Anand, B. K., and S. Dua. Indian J. Med. Res. 49: 834-836, 1961.
9. Anand, B. K. , S. Dua, and G. S. Chhina. Indian J. Med. Res. 46:
277-287, 1958.
10. Andersson,
B., C. C. Gale, and J. W. Sundsten. Acta Physiol.
Stand. 55: 177-188, 1962.
11. Andersson,
B., and S. M. McCann. Acta Physiol. Stand. 33: 333346, 1955.
12. Andersson,
B., and B. Larsson. Acta Physiol. Stand. 52: 75-89,
1961.
13. Andersson,
B., and S. Larsson. Acta Physiol. Stand. 38: 22-30,
1957.
14. Andersson,
B. , and S. Larsson. Pharmacol.
Rev. 13: 1-16, 1961.
15. Baillie,
P., and S. D. Morrison.
J. Physiol. (London) 165: 227-245,
1963.
16. Brobeck, J. R. Recent Progr. Hormone Res. XVI: 439-466, 1960.
17. Brobeck, J. R. Yale J. Biol. Med. 20: 545-552, 1948.
18. Brobeck, J. R., S. Larsson, and E. Reyes. J. Physiol. (London)
132: 358-364, 1956.
and C. N. H. Long. Yale J. Biol.
19. Brobeck, J. R. , J. Tepperman,
Med. 15: 831-853, 1943.
20. Brooks, C. McC. Am. J. Physiol. 147: 708-716, 1946.
21. Chalmers,
T. M., G. L. D. Pawan, and A. Kekwick. Lancet II:
3-12, 1960.
22. Crow, L. T. In: Thirst, edited by M. J. Wayner. Oxford: Pergamon
Press, 1964, pp. 473-486.
23. Davidson, I. W. F. , J. M. Salter, and C. H. Best. Am. J. Clin.
316
THE PHYSIOLOGIST
Nutr. 8: 540-546, 1960.
24. Delgado, J. M. R., and B. K. Anand. Am. J. Physiol. 172: 162168, 1953.
25. Epstein, A. N. J. Comp. Physiol. Psychol. 52: 37-45, 1959.
26. Epstein, A. N. Science 131: 497-498, 1960.
27. Epstein, A. N., and P. Teitelbaum.
Science 132: 1491, 1960.
28. Epstein, A. N., and P. Teitelbaum.
In: Thirst, edited by M. J.
Wayner. Oxford: Pergamon Press, 1964, pp. 395-410.
29. Fisher, A. E., and J. N. Coury. Science 138: 691-693, 1962.
30. Fryer, J. H. Am. J. Clin. Nutr. 6: 354-364, 1958.
31. Green, J. D., C. D. Clemente, and J. de Groot. J. Comp. Neurol.
108: 505-545, 1957.
32. Greer, M. A. Proc. Sot. Exptl. Biol. Med. 89: 59-62, 1955.
33. Gregersen,
M. I. , and L. J. Cizek. In: Medical Physiology, edited
by P. Bard. 11th ed. St. Louis: C. V. Mosby, 1961, Ch. 17,
pp. 317-331.
34. Grossman, M. I., and I. F. Stein. J. Appl. Physiol. 1: 263-269,
1948.
35. Grossman, S. P. Science 132: 301-302, 1960.
36. Grossman, S. P. Am. J. Physiol. 202: 1230-1236, 1962.
37. Grossman, S. P. In: Thirst, edited by M. J. Wayner. Oxford:
Pergamon Press, 1964, pp. 487-514.
38. Hamilton, C. L., and J. R. Brobeck. Am. J. Physiol. 203: 383384, 1962.
39. Hess, W. R., and M. Von Brugger. Helv. Physiol. Acta. 1: 33-52,
1943.
40. Hoebel, B. G., and P. Teitelbaum.
Science 135: 375-377, 1962.
41. Iggo, A. J. Physiol. (London) 128: 593-607, 1955.
42. Iggo, A. J. Physiol. (London) 131: 248-256, 1956.
43. Keller, A. D., D. M. Witt, and H. L. Batsel. Federation Proc.
18: 80, 1959.
44. Kennedy, G. C. Colloquia on Endocrinology
(Ciba) Vol. 4, edited
by G. E. W. Wolstenholme.
London: J.&Z A.ChurchiH,
1952, pp.
203-212.
45. Kennedy, G. C. Proc, Roy. Sot. Biol. B140: 578-596, 1953.
46. Koikegami,
H. , S. Fuse, S. Hiroki, T. Kazami, and Y. Kageyama.
Folia Psychiat. Neurol. Japon. 12: 207-223, 1958.
47. Larsson, S. Acta Physiol. Stand. 32: l-40, 1954.
48. Maire, F. W. Federation
Proc. 15: 124, 1956.
49. Mayer, J. Physiol. Rev. 33: 472-508, 1953.
50. Mayer, J. Nutritional
Abstracts and Reviews. 25: Pt.1, 597-611;
Pt. 2, 871-883, 1955.
51. Mayer, J. Am. J. Clin. Nutr. 8: 547-561, 1960.
52. Mellinkoff,
S. M. Ann. Rev. Physiol. 19: 193-204, 1957.
53. Miller,
F. R. Pfluger Arch. 143: l-20, 1911.
54. Miller,
N. E., C. J. Bailey, and J. A. F. Stevenson. Science 112:
256-259, 1950.
55. Montemurro,
D. G., and J. A. F. Stevenson. Can. J. Biochem.
Physiol. 35: 31-37, 1957.
56. Montemurro,
D. G., and J. A. F. Stevenson. Yale J. Biol. Med.
28: 396-403, 1955-56.
57. Morgane,
P. J. Am. J. Physiol. 201: 838-844, 1961.
58. Morgane,
P. J. Anat. Record 139: 257, 1961.
THE
PHYSIOLOGIST
317
59. Morgane,
P. J., and A. J. Kosman. Federation Proc. 16: 90, 1957.
60. Morgane,
P. J., and A. J. Kosman. Nature 180: 598-600, 1957.
P. J., and A. J. Kosman. Am. J. Physiol. 197: 158-162,
61. Morgane,
1959.
62. Morgane,
P. J., and A. J. Kosman. Am. J. Physiol. 198: 13150
1318, 1960.
63. Nielson, H. C., R. W. Doty, and L. T. Rutledge. Am. J. Physiol.
194: 427-432, 1958.
64. Olds, J. Science 12.7: 315-324,
1958.
65. Paintal, A. S. J. Physiol. (London) 126: 255-270, 1954.
66. Penick, S. B., and L. E. Hinkle. Am. J. Clin. Nutr. 13: 110-114,
1963.
67. Robinson, B. W. In: Thirst, edited by M. J. Wayner. Oxford:
Pergamon Press, 1964, pp. 411-427.
68. Robinson, B. W. , and M. Mishkin. Science 136: 260-262, 1962.
69. Robinson, B. W. , and M. Mishkin. XXII Intern. Congr. Physiol.
Sci., Leiden, 1962. Abst. 362.
70. Ruth, T. C., F. W. Maire,
and H. D. Patton. XX Intern. Congr.
Physiol. Sci., Brussels,
788-789, 1956.
71. Russek, M., and S. Pina. Nature 193: 1296, 1962.
72. Scherrer,
H. Exptl. Neurol. 2: 97-108, 1960.
73. Shapiro, B., and E. Wertheimer.
Metabolism
5: 79-86, 1956.
74. Sharma, K. N., and S. Dua. The Physiologist
6: 273, 1963.
75. Skultety, F. M., and T. M. Gary. Neurology 12: 394-401, 1962.
76. Slusher, M. A., and S. Roberts. Federation Proc. 15: 173, 1956.
77. Smith, H. W. Am. J. Med. 23: 623-652, 1957.
78. Smith, 0. A. Anat. Record 124: 363-364, 1956.
79. Smith, 0. A. In: Electrical
Stimulation of the Brain, edited by D. E.
Sheer. Austin, Texas: Univ. of Texas Press, 1961, pp. 367-370.
80. Smith, R. W., and S. McCann. Am. J. Physiol. 203: 366-370, 1962.
81. Soulairac,
A. Bull. Biol. Franc. Belg. 81: 273-432, 1947.
82. Sprague, J. M., W. W. Chambers, and E. Stellar. Science 133:
165-173, 1961.
83. Stevenson, J. A. F. Recent Progr. Hormone Res. 4: 363-394, 1949.
84. Stevenson, J. A. F. XXII Intern. Congr. Physiol. Sci., Leiden,
1962, vol. 2, Abst. 359.
85. Stevenson, J. A. F. In: Thirst, edited by M. J. Wayner. Oxford:
Pergamon Press, 1964, pp. 553-567.
86. Stevenson, J. A. F. Unpublished observations,
1963.
87. Stevenson, J. A. F., B. M. Box, and D. G. Montemurro.
Can. J.
Physiol. Pharmacol.
1964. In press.
88. Stevenson, J. A. F., B. M. Box, and A. Szlavko. Proc. Sot. Exptl.
Biol. Med. 115: 424-429, 1964.
89. Stevenson, J. A. F., D. G. Montemurro,
and L. L. Bernardis.
Federation
Proc. 17: 156, 1958.
90. Stowe, F. R. Jr., and A. T. Miller,
Jr. Experientia
13: 114-115,
1957.
Zh. SSSR Sechenov.
91. Sudakov, K. V., and S. K. Rogacheva. Fiziol.
48: 728, 1962.
Federation
Proc. 22: T306-T310,
1963. NO.&
Pt.H.
92. Sundsten, J. W., and C. H. Sawyer. Federation Proc. 19: 293, 1960.
93. Teitelbaum,
P. J. Comp. Physiol. Psychol. 48: 156-163, 1955.
94. Titchen, D. A. J. Physiol. (London) 125: 25P, 1954.
95. Traczyk, W. Acta Physiol. Polon. 13: 239-251, 1962.
318
THE PHYSIOLOGIST
96. Van Itallie, T. B. Diabetes 8: 226-231, 1959.
97. Wagner, J., L. Grunden, K. Conrey, W. Mahler, and J. de Groot.
Federation Proc. 21: 173, 1962.
98. Weil, R., and de W. Stetten, Jr. J. Biol. Chem. 168: 129-132, 1947.
99. Wolf, A. F. Am. J. Physiol. 161: 75, 1950.
100. Wood, C. D. Neurology 8: 215-220, 1958.
and R. Tarnecki.
Acta Biol. Exptl.
101. Wyrwicka, W., C. Dobrzecka,
20: 121-136, 1960.
TRAVEL GRANTS FOR TOKYO
PHYSIOLOGICAL
CONGRESS
Travel allotments will be available to scientists who are citizens
or residents of the USA who may require such assistance.
It should
be pointed out that the number of travel awards will be limited and that
persons able to finance their travel in other ways, in whole or in part,
should arrange to do so. Some degree of preference in awards will be
given to younger scientists and to persons presenting communications.
It is expected that the grant will cover round trip charter or group jet
fares.
Reimbursement
for travel within the USA may be available for
persons unable to meet such costs from other sources.
Deadline for
receipt of applications
for travel grants is 1 January 1965. Application
forms may be obtained from:
USA National Committee for the IUPS
Room 256
2101 Constitution Ave., N.W.
Washington,
D. C . 20418
Applicants will be responsible
registration,
travel arrangements,
for their own passports,
and hotel reservations.
visas,
The deadline for registration
for the Congress is 1 February, 1965.
For those who have not already registered,
registration
forms are
available from :
Prof. Genichi Kate, Chairman
The Organizing
Committee
XXIII International
Congress of Physiological
Sciences
Department of Physiology
Keio University School of Medicine
Shinjuku - ku, Tokyo, Japan
Cable address : SCIENCOUNCIL
TOKYO
REGULATION
OF PULMONARY
VENTILATION*
FRED S. GRODINS
When Dr. Rahn invited me to give this introductory
talk, I accepted
only because he stated that its purpose was “to bring the non-specialist
up to date and make it easier for him to obtain an over-all or more
general view of present research trends in the area of control of respiration. ” This prescription
seemed to exactly fit my own needs in
this area, and I hope my efforts to educate myself will assist those of
you who feel a similar need.
Ever since Legallois (28) discovered a medullary respiratory
center
in 1812, its responses to various neural and chemical inputs have been
studied.
Since it was known from the time of Lavoisier that the primary
function of respiration
was 02 procurement
and CO2 elimination,
it was
natural to begin the study of chemical agents with these. It also seemed
natural to assume that the effective concentrations
of these agents resided in the arterial blood which supplied the center.
Controversy is
nothing new in this field! In 1882, Rosenthal (46) using only narcotic
levels of CO2 in his experiments,
decided that 02, not CO2, was the
important agent. Miesscher-Rilsch
(36), in 1885, using more moderate
concentrations
of CO2 and 02 in man, made the opposite choice.
Miesscher-Rilsch’s
early decision in favor of CO2 was adopted and
greatly extended by Haldane and his school beginning in 1905. Haldane
developed methods for measuring alveolar pCO2 and was impressed
both by its constancy under various conditions as well as by the great
sensitivity of ventilation to inspired CO2. In 1905, he stated that under
“normal conditions”,
the rate of alveolar ventilation depended exclusively upon the pCO2 of the respiratory
center (16). Although his “normal conditions”
included muscular exercise they excluded arterial
anoxemia.
Haldane knew of course that ventilation was increased by
arterial anoxemia, but he preferred to regard this as an “abnormal
stimulus” to the center.
This was the beginning of a trend on the part
of various respiratory
physiologists
to pick out a single factor as the
“normal”
or “true” stimulus to the respiratory
center and to assign
all others a secondary role in modifying the response to this true
stimulus.
At that time, respiratory
disturbances
in acid-base balance
were not understood,
and it was believed that the low blood CO2 content
associated with anoxemia was due to a metabolic acidosis resulting
from lactic acid production.
Since it was also known that fixed acid
injection caused hyperpnea, Haldane modified his views somewhat and
wrote in 1908 that the activity of the respiratory
center depended upon
the total acidity of the blood including carbonic acid, and that increased
*Taken from the introductory
remarks given at the session on
Regulation of Respiration
at the 1964 Federation Meetings.
The author’s original research cited in this paper was supported
in part by Research Grant H-1626 and Research Career Award 5-K6HE-14 187 from the C. S. Public Health Service.
319
320
THE PHYSIOLOGIST
blood acidity caused anoxic hyperpnea (3,17).
He still insisted, however, that ventilation was always determined by alveolar pCO2 although
oxygen lack and other conditions might alter its threshold exciting value
(17) .
In 1911, consistent with the then current belief that anoxemia was
associated with acidemia,
Winterstein
(49) proposed his “first reaction
theory”.
He stated that “neither pO2 nor pC02\as such but only the
(H+) of the blood influences the chemical regulation of breathing..
..
This theory places the whole chemical regulation of breathing (02 lack
as well as CO2 excess and deficit) upon a single unitary cause. ” It is
worth noting that Winterstein
fully appreciated and eloquently stated
the fallacy of arbitrarily
choosing a “true” stimulus (49, 50). Although
perhaps superficially
resembling
this, his proposal was really quite
different in concept, i. e., it suggested a common chemical path through
which each of the different chemical stimuli could operate.
But shortly thereafter another fallacy, that of anoxic acidemia, was
revealed by Winterstein
himself (50) Haggard and Henderson (15) and
others.
It turned out that arterial
(H+) was low, not high, in arterial
anoxemia!
Winterstein’s
resourcefulness
was equal to the challenge,
however, for in 1921 he proposed his second reaction theory which retained the importance of (H+) but now placed its effective concentration
inside the cells of the respiratory
center and thus beyond measurement
(51). This concept was adopted and extended by Gesell in 1925 (10).
Then, in the early 1930’s, the necessity for postulating an increased (H+)
either in the blood or inside the cells of the respiratory
center to explain
anoxic hyperpnea was removed when Heymans demonstrated
the role of
the carotid and aortic chemoceptors
(19).
A new period began in 1936 when Nielsen (40) published a monumental
study on the chemical regulation of human respiration
which aimed, among
other things, to decide whether the “true” stimulus to the center was
CO2, as postulated by Haldane, or (H9 as postulated by Winterstein
and
Gesell.
His conclusion in favor of CO2 was based on a decision process
so strange that it deserves careful description.
Nielsen adopted Lindhard’s method of measuring the excitability
of the respiratory
center
(32), an apparently innocent procedure illustrated
in fig. 1. Under a
particular
condition (say NH4Cl acidosis), we measure the subject’s
ventilation and alveolar pCO2 when breathing air (point B), and when
breathing a CO2 mixture (point C). We then define the excitability
of
the center as the slope, not of the line ABC, but rather of the transformed line, OP, in the right hand plot where the axes are now @R/R)
and A V. Even this looks innocent enough until we ask what the numerical
value of this slope turns out to be. It doesn’t take much of a trigonometer
to realize that the ventilation at B li. e. the “initial value” or TTAusgangsversuch”) is equal to Rtan 0= R($$), the same as the slope of OP and thus
the excitability
of the center! We-arrive at the remarkable
result that
the excitability
of the center under any condition other than CO2 inhalation is simply the value of the ventilation!
Having defined excitability
in
this way, we really don’t need to do any more experiments
or go to the
trouble of determining
these CO2 response curves at all, for it is inevitable that anything other than CO2 inhalation which increases ventilation
THE PHYSIOLOGIST
321
can only do so by increasing the excitability
of the center.
Nielsen decided that because a given (H+) produced less hyperpnea in NH&l acidosis than in CO2 inhalation despite an increased excitability
of the
center in the former, H+ could not be regarded as the adequate chemical
stimulus to breathing and this role must be assigned to C02.
AV
Fig. 1. Lindhard-Nielsen
method for measuring the
excitability
of the respiratory center.
It turned out that this misadventure
in definitions had a happy result it stimulated my colleague,
John Gray, to develop his multiple factor
theory of respiratory
regulation (ll), a contribution
which has greatly
influenced research in this field ever since. This theory had three important features.
First, it was quantitative in concept with rigorous
definitions and explicitly
stated assumptions.
Second, it refused to concern itself either with non-measurable
hypothetical intracellular
mechanisms or with the fruitless subjective game of choosing a single true stimulus from several equally qualified candidates.
Instead, like the early
German school of Zuntz, it accepted the obvious common sense notion
that many different chemical stimuli were carried to central or peripheral receptors by the arterial
blood, and that the resulting ventilation
itself to steady state conwas a function of all of them. By restricting
ditions, it could measure the effective concentrations
of these stimuli
in arterial blood without having to worry about the nature of any ultimate
but as yet unmeasurable
intracellular
mechanism.
Finally, it recognized
that the respiratory
system was a closed-loop
regulator (fig. 2) in which
not only did the chemical stimuli determine the level of ventilation through
the controlling
system, but the level of ventilation determined the concentration of the chemical agents via the controlled
system, and that
these concentrations
were interdependent
(fig. 3).
Gray first tried to obtain a controller
equation restricted
to two independent variables,
arterial pCO2 and (H+), which would work for both
CO2 inhalation and metabolic disturbances
in acid-base balance.
He
started with the simplest guess, namely that the effects of pCO2 and (H+)
were independent and additive.
There was nothing sacred about this
guess. It was retained only because it turned out to work!
Since its
322
THE PHYSIOLOGIST
Fig. 2. The closed-loop
respiratory
chemostat.
(From Grodins and James.
Ann. N.Y. Acad. Sci. 109:
852-68, 1963).
Fig. 3. The interdependence
of the arterial
chemical
agents.
L ------
J
----------
validity was supported by two different conditions in which the pattern
of pCO2 - (H’) behavior was quite different, faith in its generality was
strengthened,
and this encouraged Gray to extend it to include arterial
anoxemia.
This extension was done in such a way that it could not fail
to work whether the assumption of independence and additivity were
valid or not provided its application was restricted
to arterial anoxemia
alone, i. e. to the same data on which its derivation was based. An independent test of its general validity would have required data on combinations of anoxemia and CO2 inhalation or metabolic disturbances
in
acid-base balance, but such data were not available.
This then was the
weakest point of the theory.
This brings us to what we might call the present era. We shall only
have time to look very briefly at some selected highlights,
and I apologize
in advance for the unavoidable omission of other equally important contributions.
The current research trends we shall consider can be classified under four major headings:
1. Interaction
between
stimuli
and the quantitative
approach.
THE
PHYSIOLOGIST
2. Mechanism
receptors.
3. Dynamic
323
of central
sensitivity
models of respiratory
4. The hyperpnea
- the CSF and intracranial
regulation.
of exercise.
Interaction between stimuli.
Gray’s best tested assumption,
i. e.
that the pCO2 and (H’) effects were independent and additive, appears
to have been validated by several workers including Perkins (43),
Katsaros (24), Lambertsen
(26), and Saito (47), although there seems
to be a dissenting note scheduled for presentation
here this afternoon
(18). On the contrary,
his essentially untested assumption that the
pO2 effect was also independent and additive has been consistently denied, first by Nielsen and Smith in 1951 (41) and subsequently by Lloyd
and Cunningham (33) and by Loeschcke (35). The crucial data of Nielsen
and Smith are shown in fig. 4. If Gray’s assumption were valid, the
three lines should have been straight and nearly parallel.
Cunningham’s
group (33) confirmed and extended these results and chose to represent
the linear portion of such curves as a family of straight lines whose
slope parameter was a hyperbolic function of alveolar p0 as shown in
2
fig. 5. They then formulated the general problem of respiratory
regulation as one of determining
the effect of various agents upon the four
A, B, C, and D. This they have proceeded to do over the
parameters,
past several years testing among other things, acidemia,
hyperthermia,
and norepinephrine
. In so doing they have recognized the general importance of a quantitative mathematical
approach to complex control problems, but it should be clear that their particular
representation
is a
purely arbitrary
one which refuses to break the seal of Pandora’s Black
Box!
This might be the place for a word of caution about conclusions based
on the slope of the so-called CO2 response curve. Cunningham thought
that if pO2 were an independent and additive stimulus,
Gray’s theory
required these curves at different constant levels of pO2 to be parallel,
but you will note that we said “nearly parallel”.
Why the difference?
The CO2 response curve is a composite response to pCO2 and (H+), and
anything that changes the relationship
between these two variables through
the blood buffer systems will alter the curve. A reduction in 02 saturation increases the buffer capacity for CO2 so that a given change in pCO2
would produce less change in (H+). Hence Gray’s theory really predicts
that the slope of the CO2 response curve should decrease at low ~02,
and thus the discrepancy between theory and observation was even greater
than Cunningham thought it was. He was lucky - it might have turned out
the other way. 1 I think the moral is obvious - do not neglect the composite
nature of the CO2 response curve.
Mechanism of central sensitivity.
Interest in the intimate mechanisms
by which changes in arterial pCO2 and (H+) ultimately
effect the respiratory center received new impetus in the early 1950’s when Leusen (29,30)
showed that an increased (H+) in CSF perfusing the cerebral ventricles
stimulated ventilation.
It was first believed that this effect was exerted
directly upon the respiratory
center.
However, Loeschcke (34) showed
324
THE PHYSIOLOGIST
Fig. 4. Ventilation
as a function
of alveolar pCO2 at three dif ferent alveolar pO2 values:
(X), pO2=169; (0), pO2=110;
(+), p02=4?; (.), pO2=3’7. (From
Nielsen and Smith. Acta Physiol.
Stand. 24:293-313,
1951).
that local application of acid to the floor of the fourth ventricle failed
to stimulate breathing,
and he postulated the existence of a chemosensitive area outside the centers which was bathed in CSF. Extending this
work, Mitchell (38) and coworkers
identified paired chemosensitive
areas on the ventrolateral
surface of the medulla in the cat (fig. 6).
They are bounded medially by the pyramidal tracts, laterally by the
roots of the 8th-11th cranial nerves, rostrally by the pons and extend
of pledgets containing CSF
some 5- 6 mm caudally . Local application
equilibrated
with high pCO2 and (H+) or containing nicotine or acetyl
choline produced prompt hyperpnea, whereas local cooling or procaine
325
THE PHYSIOLOGIST
/NT-ERh’AL
AUDITORY
ARTER
ANTEUIOR
CERCBELLAR
Nl?n
iNFER,OR’
ARTERYNzr-NH-4
BASILAR
ARTERY
ROSTER/OR
CERE8ELLAR
u
-
/,VFER
A
(6
16
NHll
VERMUUAL
__Rp_II-
(7
ARTERY
I
I
l6
RIGWT
If
11
8766432l0123r
If
[
11
LtFT
”
I
(9
“1’
20
Cb678
(From Mitchell,
Fig. 6. Location of the medullary chemoreceptors.
Loeschcke, Severinghaus,
Richardson,
and Massion.
Ann. N. Y. Acad.
Sci. 109(2): 661-81,1963).
326
THE PHYSIOLOGIST
application depressed respiration
usually to the point of apnea. Similar
responses were produced by perfusing the solutions into the subarachnbid
space over the ventrolateral
surfaces of the medulla.
Because proportionate increases in pCO2 and (HCO$), (i.e. constant (H+) perfusion),
depressed ventilation,
these workers believed this sensitive area to be
an H+ receptor.
However, since the blood-brain
barrier
is freely permeable to CO2 but not to H+ or HC03, acute changes in CSF (H+) are
mainly a reflection of changes in blood pCO2, and the authors postulated
that all medullary CO2 sensitivity was mediated via these CSF H+ receptors on the ventrolateral
surfaces of the medulla.
Thus, just as
Heymans showed in the early 1930’s that the respiratory
response to
pO2 was mediated via “distant” peripheral
receptors in the carotid and
aortic bodies, it now appears that Loeschke has demonstrated
that the
response to pCO2 is mediated via “close”, but still peripheral,
receptors bathed in CSF.
It is not at all clear to me just what role these investigators
assign
their receptor in acute metabolic disturbances
in acid-base balance.
Here several authors have shown that CSF (H+) changes only very slowly
and then in a direction opposite to that of blood (H+)(5,31,45).
Do both
blood and CSF somehow compete for the attentions of this single receptor, or are there two receptors,
one responding to CSF (H+) and the
other to blood (H+) as suggested by Lambertsen
(27)? Some such explanation seems necessary.
Dynamic models of respiratory
regulation.
Gray’s theory was limited
to the steady state. As such, it could ignore the ultimate mechanism by
which changes in arterial
pCO2, (H+), and pO2 influenced ventilation,
merely assuming that the arterial concentrations
of these agents have a
constant relationship
to the effective levels of the actual stimuli at the
receptor sites whatever and wherever these might be. We hope ultimately to be able to treat such steady state behavior as a special case
of a more general dynamic analysis.
Such an analysis is very difficult.
It requires all of the information
needed for a steady state analysis and
Some 10 years ago when we were considerably
more
much more besides.
rash and ignorant than we are now, we suggested such a model to explain
some peculiar features of the transient response to CO2 inhalation (14).
Although this model ignored many more details than it included, it did
assign the effective pCO2 to the tissues of the respiratory
center and
was surprisingly
successful in accounting for much of the observed behavior.
In the last few years, this very crude model has been refined
and extended by several workers (6, 20,37).
In general, these models
include many of the details neglected in our earlier one. Among these
of the tissue reservoir,
are other stimuli (H+ and pO2), “unlumping”
dependence of cerebral blood flow on arterial pCO2, blood transport
lags to and from various receptor sites, the blood-brain
barrier,
and
others.
It is obvious that our understanding
of respiratory
regulation
must ultimately
be expressed in this form. It is equally obvious that
we still have a long way to go, but mutual feedback between models of
this sort and experimental
results should speed the journey.
The hyperpnea of exercise.
Last but far from least we come to the
I think Carl Schmidt stated the case precisely
hyperpnea of exercise.
THE PHYSIOLOGIST
in his introductory
remarks
years ago (48) when he said
tory control is its ability to
100 odd years of effort, I’m
327
to a New York Academy symposium two
that the real test of any concept of respiraexplain the hyperpnea of exercise.
Despite
not sure we can pass this test yet!
Let us begin with Haldane’s view cast in modern control terminology
as our point of departure (fig. 7). If we increase MIQO2 without changing ventilation,
arterial pCO2 must rise. This in turn would stimulate
ventilation and the final steady state operating point at any given MHcO~
would be determined by simultaneous
solution of the controller
and proBecause this is a proportional
controller
(i.e. its recess equations.
sponce depends only on the present level of the input and not at all on its
past history), there will be some steady state increase or “error”
in
pCO2 whose magnitude will vary inversely with controller
gain. This
is a very attractive explanation.
It is simple, requires no exotic stimuli,
and provides an automatic adjustment of ventilation to metabolism.
True,
the adjustment would fall short of perfection to the extent that the controller gain fell short of infinity, but a reasonably sensitive controller
would provide a very satisfactory behavior.
Fig. 7. Closed-loop
pCO2 regulator.
arterial
Unfortunately
it has turned out that if we judge controller
gain by its
response to CO2 inhalation at rest, then the error observed in moderate
exercise is nowhere near enough to account for the ventilation (12). The
apparent failure of this admirably simple explanation has launched a
vigorous search for others.
For a long time such studies moved along lines outlined by Geppert
and Zuntz (9) in 1888. If there are other stimuli,
they must influence
the center via neural and/or humoral paths. If neural, they may originate centrally (e.g. the TTcortical radiation”
of Krogh (25), or peripherally in the exercising limbs (e.g. in kineceptors,
chemoceptors,
thermoceptors,
‘ergoceptors’,
‘X-ceptors’).
If humoral, they most
likely originate in the exercising
muscles.
Many attempts to explore
these possibilities
have been made in both animals and man using electrically induced exercise, vascular occlusion, denervation,
and cross
Investigators
most closely incirculation
procedures among others.
volved in such studies include Krogh and Lindhard (25), Asmussen and
Nielsen (2,42), Comroe and Schmidt (4), Kao (21-23), Dejours (7,8)
Despite many errors in interpretation,
certain conclusions
and others.
seemed justified from these studies: 1) A neural factor must be responsible
THE PHYSIOLOGIST
328
for the initial increase in ventilation simply because it occurs so rapiddead time (8)
ly, i.e., well within the shortest relevant circulatory
(fig. 8); 2) A neural factor must operate in the steady state for its abrupt
disappearance
is the only way to account for the very rapid fall in ventilation when exercise is stopped (8) (fig. 8); 3) At least part of the steady
state neural factor must arise peripherally
for cross circulation
studies
show that a center communicating
with an exercising limb only via the
blood produces less ventilation than one which has both humoral and
neural communication
channels intact (21-23);
4) Granting the existence
of a peripheral
neural stimulus,
it might arise in kineceptors
(4, 7,8)
or hypothetical
‘ergoceptors’
(22),
but apparently not in thermoceptors
(39) .
Thus it seemed rather well established that the hyperpnea of exercise
depended upon both neural and humoral factors (8). The former certainly
had a peripheral
component and perhaps a central one as well, while the
latter represented
the combined effect of all changes in pCO2, (H+), ~02,
, Terminal
Fall
------------a-
I
Ewercice
Repc$
I0
01
21
41
J
61
TIME
12.
141
i
I
- II0
Fig. 8. Time course of ventilatory
response to exercise.
Dejours.
J. Physiol. (Paris).
51:163-261,1959).
RQcup6rSokion *
1
I
2
4 mn
(From
THE PHYSIOLOGIST
329
temperature,
epinephrine,
etc. which, although individually
small,
And of course we must always
seemed to be collectively
significant.
remember that the basic pCO2 feedback path is eternally vigilant and
will provide corrective
action or fine adjustment if the combined effect
of the other stimuli should miss the mark.
But even though it may turn out to be perfectly correct, the notion
that the very accurate adjustment of ventilation to metabolism
depends
upon a large number of factors which just happen to add up right makes
has
some physiologists
feel uneasy. 1 Hence, the search for alternatives
One,
continued, and we shall briefly mention two recent suggestions.
associated with the names of Armstrong
(1) and Riley (44) postulates a
mixed venous chemoceptor.
Unfortunately,
no one has yet been able to
conclusively
demonstrate its existence, and Kao’s cross circulation
experiments
would seem to deny its importance (22,23).
Fig. 9. Theoretical
dynamic behavior
exercise, and during CO2 inhalation.
N.Y. Acad. Sci. 109:852-68,1963).
of alveolar pCO2 at rest, during
(From Grodins and James. Ann.
330
THE
PHYSIOLOGIST
A completely new and intriguing
possibility
has been suggested by
Yamamoto (52). Its essence is that we may be wrong in judging the
pCO2 gain of the center in exercise by its response to CO2 inhalation
at rest. Yamamoto pointed out that the dyanmic behavior of alveolar
pC0 is much different in exercise than at rest or during CO2 inhalation 2ifig. 9) and that such dynamic information
might provide the signal
responsible
for exercise hyperpnea.
Perhaps the most disturbing
thing
of all about this suggestion was that it was made to account for a crucial
experimental
observation by Yamamoto and Edwards (53). They had
found that if the systemic venous blood of rats were artificially
loaded
with CO2, steady state ventilation responded exactly in proportion
to
the load, just as in normal moderate exercise.
This finding directly
contradicts
the results of a variety of denervation (13) and cross circulation (21-23) experiments.
Its implications
are so important that I
would assign highest priority to resolving this apparent conflict at the
observational
level.
And so we come to the end of our brief account of past history and
current trends in research on the regulation of breathing.
Although it
is probably safe to say that we know more about it now than we did 100
years ago, it is also true that many of the old problems remain unsolved
and new ones constantly arise.
There is a lot to be done and we had best
get at it.
REFERENCES
1. Armstrong,
B. W., H. H. Hurt, R. W. Blide, and J. M. Workman.
The humoral regulation of breathing.
Science 133:1897-1906,196l.
2. Asmussen, E., E. H. Christensen,
and M. Nielsen.
Humoral or
nervous control of respiration
during muscular work? Acta Physiol.
Stand. 6:160-167,1943.
The effects of low atmospheric
3. Boycott, A. E., and J. S. Haldane.
pressure on respiration.
J. Physiol. (London) 37:355-77,1908.
4. Comroe,
J. H., Jr.,
and C. F. Schmidt.
Reflexes from the limbs
as a factor in the hyperpnea of muscular exercise.
Am. J. Physiol.
138:536-47,1943.
5. De Bersaques,
J., and I. Leusen.
Acid-base equilibrium
between
blood and cerebrospinal
fluid. J. Physiol. (London) 126:14P,
1954.
6. Defares, J. G., H. E. Derksen, and J. W. Duyff. Cerebral blood
flow in the regulation of respiration.
Acta Physiol. Pharmacol.
Neerl.
9:327-360,196O.
7. Dejours,
P. La regulation de la ventilation au tours de l’exercise
musculaire
chez l’homme.
J. Physiol. (Paris) 51:163-261,1959.
8. Dejours,
P. The regulation of breathing during muscular exercise
in man. A neuro-humoral
theory. In: The Regulation of Human
Respiration,
edited by D. J. C. Cunningham and B. B. Lloyd.
Oxford: Blackwell,
1963, pp. 535-47.
9. Geppert, J., and N. Zuntz. Uber die Regulation der Athmung. Arch.
Ges. Physiol. 42:189,
1888.
10. Gesell, R. The chemical
regulation of respiration.
Physiol. Rev.
5:551-595,1925.
11. Gray, J. S. The multiple
factor theory of respiratory
regulation.
AAFSAM Project Report No. 386 (1,2,3),
1945.
THE PHYSIOLOGIST
331
12. Grodins, F. S. Analysis of factors concerned in the regulation of
breathing in exercise.
Physiol. Rev. 30:220-39, 1950.
13. Grodins, F. S., and D. P. Morgan.
Regulation of breathing during
electrically
induced muscular work in anesthetized dogs following
transection of spinal cord. Am. J. Physiol. 162:64-73,195O.
14. Grodins, F. S., J. S. Gray, K. R. Schroeder,
A. L. Norins, and
R. W. Jones. Respiratory
responses to CO2 inhalation.
A theoretical study of a non-linear
biological
regulator.
J. Appl. Physiol.
7:283-308,1954.
15. Haggard, H. W., and Y. Henderson.
Hemato-respiratory
function.
III. The fallacy of asphyxial acidosis.
J. Biol. Chem. 43:3-13,192O.
16. Haldane, J. S., and J. G. Priestly.
The regulation of the lung
J. Physiol. (London) 32:225-266,1905.
ventilation.
17. Haldane, J. S., and E. P. Poulton.
The effects of want of oxygen
on respiration.
J. Physiol. (London) 37:390-407,1908.
18. Hamilton, R. W. , Jr., and E. B. Brown, Jr. Variations
in respiratory response to CO2 at different constant levels of blood pH.
Federation Proc. 23:259,1964.
19. Heymans, C., J. J. Bouckaert,
and P. Regniers.
Les sinus
carotiden.
Paris: G. Doin & Cie, 1933.
20. Horgan, J. D., and R. L. Lange. Simulation of the chemical and
circulatory
factors in the dynamic analysis of the human respiratory
control system. Digest 15th Ann. Conf. on Engineering
in Med. and
Biol., Nov. 1962, p. 53.
21. Kao, F. F., and F. S. Grodins.
Regulation of breathing during
exercise. Federation
Proc. 11:80,1952.
22. Kao, F. F. An experimental
study of the pathways involved in
exercise hyperpnea employing cross -circulation
techniques.
In:
The Regulation of Human Respiration,
edited by D. J. C. Cunningham
and B. B. Lloyd. Oxford: Blackwell,
1963, pp. 461-502.
23. Kao, F. F., C. C. Michel, S. S. Mei, and W. K. Li. Somatic
afferent influence on respiration.
Ann. N. Y. Acad. Sci. 109(2):
696-710,1963.
24. Katsaros, B., H. H. Loeschcke, D. Lerche, H. SchUnthal, and N.
Hahn. Wirkung der Bicarbonat-Alkalose
auf die Lungenbelilftung
beim Menchen.
Bestimmung der Teilwirkungen
con pH und CO2 Druck auf die Ventilation
und Vergleich mit den Ergebnissen
bei
Acidose.
Arch. Ges. Physiol. 271:732-47,196O.
The regulation of respiration
and
25. Krogh, A. , and J. Lindhard.
circulation
during the initial stages of muscular work. J. Physiol.
(London) 47:112-136,1913,
-14.
26. Lambertsen,
C. J., S. J. G. Semple, M. G. Smyth, and R. Gelfand.
H+ and pCO2 as chemical factors in respiratory
and cerebral circulatory control.
J. Appl. Physiol. 16:473-84,196l.
27. Lambertsen,
C. J. Factors in the stimulation
of respiration
by
carbon dioxide.
In: The Regulation of Human Respiration,
edited by
D. J. C. Cunningham and B. B. Lloyd. Oxford: Blackwell, 1963,
pp. 257-276.
28. Legallois,
C. J. Experiences
sur le principe de la vie. Paris, 1812.
29. Leusen, I. Chemosensitivity
of the respiratory
center.
Influence
of CO2 in the cerebral ventricles on respiration.
Am. J. Physiol.
176:39-44,1954.
of the respiratory
center.
Influence
30. Leusen, I. Chemosensitivity
332
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
THE PHYSIOLOGIST
of changes in the H+ and total buffer concentrations
in the cerebral
ventricles on respiration.
Am. J. Physiol. 176:45-51,1954.
Leusen, I. Acid-base equilibrium
between blood and cerebrospinal
fluid. Am. J. Physiol. 176:513-16,1954.
Lindhard,
J. On the sensitivity of the respiratory
center in exercise.
Arbeitsphysiol.
7:72 -, 1934.
A quantitative approach
Lloyd, B. B., and D. J. C. Cunningham.
to the regulation of human respiration.
In: The Regulation of Human
Respiration,
edited by D. J. C. Cunningham and B. B. Lloyd.
Oxford: Blackwell,
1963, pp. 331-349.
Loeschcke, H. H., and H. P. Koepchen.
Versuch zur Lokalisation
des Atmungs - und Kreisaufwirkung
von Novocain im Liquor cerebrospinalis.
Arch. Ges. Physiol. 266:628,1958.
Loeschcke, H. H., and K. H. Gertz.
Einfluss des 02 Druckes in
der Einatmungsluft
auf die Atemtatigkeit
des Menschen, geprtfft
unter Konstanthaltung
des alveolaren CO2 - Druckes.
Arch. Ges.
Physiol. 267:460-77,1958.
Miesscher-Etlisch,
F. Bemerkungen
zur Lehre von den Athembewegungen.
Arch. Physiol. 355,1885.
Milhorn,
H. T. Jr., and A. C. Guyton. Mathematical
models of
the human respiratory
control system. Federation Proc. 23(2):
307,1964.
Mitchell,
R. A., H. H. Loeschcke, J. W. Severinghaus,
B. W.
Richardson,
and W. H. Massion.
Regions of respiratory
chemosensitivity on the surface of the medulla.
Ann. N. Y. Acad. Sci.
109 (2): 661-81,1963.
Morgan, D. P., F. Kao, T. P. K. Lim, and F. S. Grodins. Temperature and respiratory
responses in exercise.
Am. J. Physiol.
183:454-58,1955.
Nielsen, M. Untersuchungen
Giber die Atemregulation
beim Menschen.
Skand. Arch. Physiol. 74, Suppl. 10:83-208,1936.
Nielsen, M., and H. Smith. Studies on the regulation of respiration
in acute hypoxia.
Acta Physiol. Stand. 24:293-313,195l.
Nielsen, M., and E. Asmussen.
Humoral and nervous control of
breathing in exercise.
In: The Regulation of Human Respiration,
edited by D. J. C. Cunningham and B. B. Lloyd. Oxford: Blackwell,
1963, pp. 503-513.
Perkins, J. F. Jr. Arterial
CO2 and hydrogen ion as independent,
additive respiratory
stimuli: support for one part of the Gray multiple
factor theory.
In: The Regulation of Human Respiration,
edited by
D. J. C. Cunningham and B. B. Lloyd.
Oxford: Blackwell, 1963,
pp. 303-317.
Riley, R. L. The hyperpnea of exercise.
In: The Regulation of
Human Respiration,
edited by D. J. C. Cunningham and B. B. Lloyd.
Oxford: Balckwell,
1963, pp. 525-534.
Robin, E. D., R. D. Whaley, C. H. Crump, A. G. Bickelmann,
and
D. M. Travis.
Acid-base relations between spinal fluid and arterial
blood with special reference to control of ventilation.
J. Appl. Physiol.
13:385-92,1958.
Rosenthal, I. In Hermanns Handbuch der Physiologie.
Leipzig,
1882,
w/2:269-286.
Saito, K., Y. Honda, and N. Hasamura.
Evaluation of respiratory
response to changes in PC02 and hydrogen ion concentration
of
THE PHYSIOLOGIST
48.
49.
50.
51.
52.
53 .
333
arterial blood in rabbits and dogs. Japan. J. Physiol. 10:634-45,
1960.
Schmidt, C. F. Introductory
remarks - six score years of chemoreflexes.
Ann. N. Y. Acad. Sci. 109(2):631-3,1963.
Winterstein,
H. Die Regulierung der Atmung durch das Blut. Arch.
Ges. Physiol. 138:167-184,191l.
Winterstein,
H. Neue Untersuchungen
uber die physikalisch-chemische
Regulierung
der Atmung.
Biochem. Z. 70:45-72,1915.
der Atmungsregulation.
Arch.
Winterstein,
H. Die Reaktionstheorie
Ges. Physiol. 187:293-298,192l.
Yamamoto, W. S. Mathematical
analysis of the time course of
alveolar C02. J. Appl. Physiol. 15:215-219,196O.
Yamamoto, W. S., and M. W. Edwards, Jr. Homeostasis of carbon
dioxide during intravenous infusion of carbon dioxide.
J. Appl.
Physiol. 15:807-818,196O.
AAAS MEETING
The American Association for the Advancement of Science will hold
its 13lst annual meeting in Montreal,
Canada, December 26-31,1964.
This year’s meeting will be distinctive
in several respects; its locale,
the proportion
of distinguished
speakers from abroad, and the overall
high quality of the special sessions and symposia.
A series of special
sessions will be concerned with “Moving Frontiers
in Science” with
world-renowned
speakers.
There will be an international
conference
and a series of sessions on Communication
and Social Interaction in
Primates. 7’ These special sessions and symposia along with the regular
section session papers should make this AAAS meeting most attractive
to physiologists.
BIOPHYSICAL
SOCIETY
MEETING
The 9th Annual Meeting will be held February 24, 25, 26, 1965 at
the Sheraton- Palace Hotel, San Francisco,
California.
Contributed
papers plus Symposia on Information
Transfer in Biological
Sys?ems
and Evolution and Exobiology will constitute the program.
Further
information
may be obtained from Dr. William Sleator, Washington
University School of Medicine,
St. Louis 10, Missouri.
PAST-PRESIDENT’S
HERMANN
Physiologists
ADDRESS
HAHN
and the Information
Crisis
Since its beginnings physiology has been in the center of biological
foment. It spawned biochemistry,
pharmacology,
and more recently
biophysics and biomathematics.
Physiology and its sister sciences have
now passed the long lag of the incubation period and are firmly entrenched in the exponential growth phase. Physiology is no longer merely
acknowledged,
but actively courted by the public, the federal agencies,
and the medical profession.
The last war was the final turning point
and we are now in the saddle as “Physiologists
on Horseback” (5).
This rapid growth has brought on many adjustments but all the kinks
have not been straightened
out. Compared with the meager pre-war
days when research was done at the enthusiastic
amateur level, it has
become now an assembly line geared to production.
This rapid development has been precipitated
by non-university
support of biological
research. Since 1945 this support has increased 20.fold.
Today we may
appear to be affluent; to paraphrase Will Rogers, “It is easy to be a
gentleman when you have a grant. ”
However, a gentleman has a conscience and assumes responsibilities.
Fortunately I am allowed to give you my
These I should like to discuss.
uncensored version, for you will recall a statement in the Preliminary
Announcement
of the Fall Meeting, “Children will be entertained elsewhere during the Past-President’s
Address. ”
Affluence, in terms of research support and respect, has, however,
created new problems.
Before the war you discharged your responsibilities to the university by teaching. Universities
never planned research
as is commonly done in industry. What you did beyond your teaching was
of relatively little concern.
Today, universities
need outside research
support in order to survive, and frequently this tail wags the dog. Support
Deans become haunted businessmen appeasing
is equivalent to survival.
the president.
Departmental
chairmen have become ornery, hard-boiled
production managers more familiar with airline schedules than teaching
Their prestige is proportional
to the number of days spent
schedules.
in Washington.
At home there is only time for reports and indulging in
toothpaste containing food particles advertised for “People who are too
busy to eat between brushings.”
This description
fits to some degree
all members of a faculty.
No wonder that the serenity of the pre-war
days is gone and that our personalities
have changed.
Professors
are
only a shade better than departmental
chairmen,
who in turn are only
slightly better than deans. These facts are now commonly recognized,
but that they have penetrated into the wildest places of New Guinea was
quite a shock.
Three summers ago I had joined Pete Scholander on an expedition
in the Coral Sea. We had caught a very large sea turtle on one of the
islands and were anxious to bring it back to camp.
Only he could have
334
THE PHYSIOLOGIST
335
persuaded me to hang onto it in the bow of an eight-foot dinghy while he
manipulated
an outboard motor at the stern. I never did manage to pull
it on board; so I was left hanging over the bow with a struggling 200.
pound turtle in my arms while Pete tried to run the surf. How we made
it I will never know. However, the small boat was so unbalanced that
we missed the channel, lost our way, and hours later reached a strange
coast where we were welcomed by natives who carried us exhausted into their hut. When we recovered I motioned with my hands that I was
hungry.
To my great surprise they answered in English, “Here is a
menu. ” When I read the bill of fare, unfortunately
quite legible, I lost
my appetite:
Fried Instructor of Physiology ......
Broiled Assistant Professor ........
Sauteed Full Professor .............
Stewed Departmental
Chairman .....
$1.00
1.25
1.50
10.00
After recovery from my initial shock I became intrigued by the great
price junp from $1.50 for Full Professors to $10.00 for Departmental
Chairmen.
I finally screwed up my courage and in a rather tremulous
voice inquired why departmental
chairmen were so expensive. A rather
tall man only returned a smile and finally said, “Have you ever tried to
clean one? ” For several years thereafter I wondered what the price of
a dean would have been.
Thus the outside support has changed our personality.
It has also
split our loyalty between the university where we feel secure and the
federal agency which we must acknowledge.
And finally, it has produced an information
explosion.
What we are now beginning to feel is
the last phase, as a necessary consequence, the communication
crisis.
Having accepted this natural development,
we must also ask what
our changing responsibilities
are. Cur divided loyalties between the
university which allows us to teach and the federal agency which allows
us to experiment have slowly been acknowledged as a new way of life for
the academician.
The information
explosion we must welcome as scientists. That it produces good, bad, and indifferent
research I believe is
inevitable as long as the support is so large.
What we have not faced is the matter of comprehending
and digesting
the ever growing accumulation
of facts. The natural reaction is a greater
and greater compartmentalization
of men and ideas with ever growing
specialization.
This tendency is fostered and encouraged today by an
ever increasing number of symposia, colloquia,
study groups, meetings,
personal communications,
exchange programs,
postdoctoral
training
programs,
and travel grants.
Specialization
does not proceed with equal
speed on all fronts.
It tends to foster cliques and prestige groups and
encourages their growth, while other areas suffer and shrink.
This is
what Price called “Little Science, Big Science” (9).
There is no question that we are all erecting higher and higher walls
of communication
barriers
around our own fields.
This is not to keep
others out, but to remain undisturbed.
This Tower of Babel must
336
THE PHYSIOLOGIST
eventually collapse and expose the nakedness of our splendid isolation.
Even within small departments
these tendencies develop. Only last
week when the members of our staff were rehearsing
their papers for
these meetings, I overheard one man remark to another, “Hermann
Rahn speaks only to Leon Farhi and Leon Farhi only to God.”
The Role of the Documentalist.
And how will the communication
crisis
be solved? To many this seems a straightforward
problem.
We build
machines, computers,
scanners, automatic printers,
translating
machines.
These in turn will be linked to smaller centers strategically
placed throughout the country.
The traditional
handlers of scientific
information,
our librarians,
editors, and publishers,
have already been
reenforced by the information
processors,
the documentalists,
computer designs, computer engineers, information
system designers,
audiovisual experts, document analysts, and a variety of other information specialists
(3). These are today a formidable
group of highly skilled experts who talk a new language, using such words as “dowsing,”
“normalization,
” “intelligence,
” “L-indexing,
” “morpheme,
” “semolanguage, ” and “associative
memory,”
and have
glyphs, ” “retrieval
acronyms ‘and abbreviations
which today outnumber the governmental
alphabet of the Rooseveltian era.
Our colleagues in the new field of scientific documentation
are forging ahead with incredible
speed. Their total budget last year for documentation research alone was approximately
25 million dollars.
They
are just beginning, their goals are concrete and well described,
their
The big monsters of their dreams will answer all
promises tempting.
your questions.
By pushing the right buttons you will obtain all you ask
for and even more. Your problem will be to avoid drowning in the flood
of information
of categorized
facts. This will undoubtedly be a godsend
for the librarian
and certainly impress the graduate student. The Medical Literature
Analysis and Retrieval System, MEDLARS,
of our National Library of Medicine is probably the first big machine which will cover
annually about 150,000 articles,
and 250,000 by 1970 (1). It will print
out for you the information
requested.
While this is obviously an important and necessary step in the communication
problem, will it really
solve it? To this I must say emphatically no.
First let me remind you that in the strict sense these machines do
not handle information,
but documents.
What to do with this information
once it arrives at your desk is the real problem.
Here we encounter a
biological computer whose efficiency, versatility,
and memory storage
are of a different order of magnitude.
It is, however, uniquely endowed
with certain unknown networks which will sort, select, reject, and associate to feed into the output on occasion, and only on occasion, new concepts, ideas, and even dreams which never existed in the primary data
which it digested.
These occasional flickers can burst into the strong
light of new concepts, and in the long run only these will justify the
whole development of our automation effort.
Today plans are big and clear, well supported and well directed with
respect to the development of mechanical computers which will categorize the primary information.
Plans are weak and ill-defined
for the
THE PHYSIOLOGIST
337
most important final step of evaluation and digestion by the biological
computer of our central nervous system.
These must go in step or we
shall eventually reach the stage where the former will control the latter.
This is really not as far-fetched as it may seem. The documentalist
will obtain the necessary data, shuffle, sort, and come up with conclusions of the state of the art in any area which you name. The next step
is obviously to point out the weaknesses in certain fields of research,
advise the federal agencies, which in turn will provide or deny financial
support in these areas. The documentalist
is unable to differentiate
between good, bad, or indifferent
research.
It is all equally acceptable
to his machine.
Nevertheless,
he can be easily tempted to assume the
role of interpreter.
His rather precise, overwhelming
statistics based
upon innumerable
bits of information
can be most convincing even though
it may or may not be based on “garbage.”
The Hole of the Physiologist.
At this juncture the scientist,
the consumer
of the product, must step in and assume a role not yet crystallized
by our
planners.
What we need is perhaps best illustrated
by the philosophy
of a certain career medical officer in our Navy who was in charge of
younger men putting in their two-year service requirements
in the
Medical Corps.
They were enthusiastic,
eager, and at times frustrated, trying to keep up with the most recent advances of the medical field.
One afternoon at the bar the Captain was drinking with his junior officers
when one of them said, “Say, Captain, how do you manage to keep up
with the literature?
” This was obviously a very loaded question since
all realized that, although the Captain did a fine job, he probably glanced
at few journals and probably had not read a medical book in years. The
bar suddenly became silent and then he said, “Jim, that* s really not
very difficult.
You see, I have a ‘garbage sifter. ’ When it has digested
the whole goll-darned
medical literature
for the year and done its sifting,
there are only one or two articles that are really worth reading. ”
While on the subject of garbage, I am reminded of an ambassador
from one of the undeveloped countries who had recently taken up his
residence in Washington.
When confronted by a local women’s club he
was asked, “Mr. Ambassador,
what has impressed you most about our
country? ” He reflected a while and answered, “The size of your garbage
cans! ” While our western prosperity has indeed allowed us to enjoy this
domestic privilege,
we are extremely undeveloped in this respect in the
Our garbage cans are too small and unless we make an
area of science.
effort to increase their size for scientific garbage we shall not only remain undeveloped but must eventually retrogress.
Others, long before, have voiced concern about the new role that we
as scientists must assume in order to rise adequately to the challenge
of the information
explosion.
Maurice Visscher (12) warned that the information problem cannot be turned over to the documentalist
but requires the active participation
of the research scientist.
Ellis Kelsey
(7) suggested that the NIH set up a senior reward system to finance individual, outstanding scientists for increased production of critical reviews.
Julius Cahn (2) warned us that the information
problem is not a housekeeping job, but must mobilize the best minds of our ablest scientists.
The Surgeon General of the Public Health Service, Luther Terry (11)
338
THE PHYSIOLOGIST
aptly phrased it this way, “In our rush to embrace the glories of automation, let us not slight the need for improvements
in traditional
methods of communication
- for example, more and better qualified evaluators, or synthesizers,
who will help us translate papers into useful
information.
” Finally I like to quote the first recommendation
from
President Kennedy’s Science Advisory Committee (lo), an excellent
document which I recommend to all. “We shall cope with the information explosion, in the long run, only if some scientists and engineers
are prepared to commit themselves deeply to the job of sifting, reviewing, and synthesizing information.
Such scientists must create new
science, not just shuffle documents.
Their activities are as much a part
of science as is tradional research.
We urge the technical community
to accord such individuals the esteem that matches the importance of
their job and to reward them well for their efforts.”
The all-important
role of the research man is clear and fortunately
has been recognized by our leaders and experts in this area. However,
the concrete proposals to enlist the support of the scientist are unclear,
vague, and unsure.
Before making a positive recommendation
The Growth of Physiology.
let me refer to Figure 1 which shows the growth of physiology.
According to our surveys it doubles approximately
every ten years. The first
complete ring represents the whole area of physiology thirty years ago,
the wedge merely a particular
area. Each decade new land was put into
cultivation doubling the area of the previous decade. This expansion is
obviously due to the increasing number of physiologists
(6). Every one
physiologist
in a given area in 1934 (see innermost dot) was joined by
one additional man in 1944 and has seven colleagues today helping him
dig new holes for the proverbial
cat described by Wallace FeM (5). In
1974 we may expect sixteen experts in this same area since our exponential growth curve shows no sign of decline (6). You will also notice that
each white field under cultivation by each physiologist
is equal when you
extrapolate it to the center of the circle.
Only the shape is changed.
While we may take pride in this continually expanding system, it also
presents cause for alarm.
Let us now consider comprehension
of an area of physiology by the
average physiologist.
This is based upon his ability to read, digest,
and distill.
This faculty, I believe, is limited and relatively fixed by
his central nervous system and therefore does not change from decade
to decade. With this assumption,
comprehension
of a particular
area
must be reduced by one-half each decade. If each white area represents
also his approximate
area of comprehension,
then you can see easily
what frightful prospects we face. Our task is to expand each decade the
central black area in our figure.
This black wedge represents the solid,
basic, digested facts and becomes the foundation of our science. While
you may quarrel with my quantitation effort, I believe the general issues
are clear.
I also want to draw attention to the task of the teacher who not only
must keep up in his reading but digest and render succinctly the advancing front of physiology.
If he spends all his efforts in this direction you
THE PHYSIOLOGIST
339
Fig.
1
can see, for example, what he faces ten years hence. I have allotted
him the area between the outer circle and the dotted line. If he must
teach more than one conventional area, his task becomes insurmountable.
What can we do? Obviously the documentalist
can help in the mechanical delivery and sorting of information.
But the final goal can only be
achieved by the scientist.
As Hallowell Davis stated (4), “There will be
an increasing
need for men who can put ideas together effectively and
write well.
These will not be a new breed of scientists.
There is no
340
THE PHYSIOLOGIST
one else but ourselves. ” Thus we must increasingly
depend upon others
for critical evaluation, and in our own field of specialization
we must
perform this function for others.
While I have quoted to you the concern of various study groups and
leaders in the documentation
area for greater participation
of the scientist, there are to my knowledge no active, concrete plans. It therefore
behooves us to take some action, as individuals,
as members of our
universities
and institutes,
as members of our Society. I am sure that
our Government is willing to support sound plans. They feel a great
responsibility
for they have contributed so much to the advancing frontier
and simultaneously
to the information
explosion.
As David Price from
the Office of the Surgeon General, Public Health Service, states (8),
“Federal Agencies have a responsibility
in furthering the communication
process.
However, the Government’s
role should not be a commanding
one, but a supporting one. Scientific societies must initiate and lead and
define the role they will play. ”
A Recommendation.
My own suggestions are that foundations and federal
agencies such as the National Science Foundation and the National Institutes of Health, with the advice of consultants,
initiate two plans of action,
One would concern itself with the training and establishment
of Career
Literature
Research Investigators;
the other would be the development
of new experimental
publications
devoted to synthesizing information
in
a manner not practiced today by reviewing journals or handbooks.
We all know talented scientists as well as teachers who excel naturally
in such reviewing and who are actually more productive in this endeavor
than in bench research.
These are the people, found in every laboratory,
whose advice is continuously sought by the active bench worker and who
frequently contribute more to the research of others than to their own.
Unfortunately
they are continuously prodded to do experimental
work instead and publish, because this is fashionable,
recognized by deans, and
helps in promotions.
To my mind this is a tremendous waste of some of
our best talent.
These people could become respected leaders in their
fields, publish magnificent reviews, solidify vague concepts, and shore
up the foundations of our science.
However, they must be well supported
and their professional
work accorded the same respect and esteem as
that of the bench worker.
Another, additional plan might be to elect each year a few of our best
and most active bench workers.
Let them go into a retreat at their home
institution or elsewhere for a period of two years.
Relieve them of all
their usual responsibilities,
and give them free reign to express themselves in their search for shoring up our foundations.
Reward them well
and develop this type of award into the most coveted prize in physiology.
Some of you will say that such work would not result in creativity.
If
this were the case I would not suggest such a plan. Creativity depends not
on what you do but where you find it. An Annual Review type article does
not require much creativity.
A Physiological
Reviews article requires
considerable
talent. What I am looking for is a step beyond this stage,
which doubly and triply distills the available information
and renders
THE PHYSIOLOGIST
341
the simple, comprehensible
essence.
This can only be done by our best
scientists,
but they need not be bench workers,
If out of every three or
four career investigatorships
we select the best man as a literature
investigator,
we can make a real step forward.
As the President’s
Science
Advisory Committee indicated (lo), ‘Such a position in science is comparable to that of a theoretical
physicist in modern day physics.”
My second proposal would be to provide new publication
vehicles for
some of the reviews which would be forthcoming under this system.
I
have in mind a format similar to that of the Scientific American.
Instead
of covering all sciences it should be started in a restricted biological
field and at a different level of sophistication.
If successful, it can enlarge its role. Many of you will say that this is far too extravagant and
gilds the lily. However, at the moment I am not concerned with cost.
This is simply an experiment no more costly than others which the taxpayer supports.
It certainly does not gild the lily. If you have read Hay
Zwemer’s review (13) of the reading habits of physiologists,
you will be
impressed with their limited capacity.
If the format and style and illustrations of a publication today are not attractive,
it simply does not get
the attention.
We are innundated with so much reading material that we
instinctively
select, and not always on a scientific basis. For example,
I have the Scientific American on the table next to my bed, but not Physiological Reviews.
This is largely a matter of competition.
The former
is so attractive in format, style, and illustration
that it actually competes
for my sleeping time. If one could develop, at a large cost I must admit,
a similar review in physiology,
it might also keep me awake at night.
This might produce sleepy physiologists;
however, a sleepy one, wellinformed, is possibly better than a wide-awake
one, uninformed.
And now I have had my say. I can leave you with good conscience to
carry on. “Old physiologists
never die, they just slowly lose their grants.”
And with farewell to this great office to which you elected me, let me once
more reiterate:
- If you are to stay on top and not become inundated in
the flood of good, bad, and indifferent information,
and if you care to direct and develop your own research area as you see it and without pressure from the documentalist’s
statistics,
then you must seize the initiative. No one else can or will do it, You must begin to train some of the
best physiologists
to act as synthesizers,
catalysts, and evaluators,
colleagues whom you will trust, respect, and accord all the honors of
a bench scientist.
To remain a well-rounded
scientist you will need their
help. You must also develop new types of publications
which will meet
the needs and supplement our traditional
approaches; and, finally, you
must show your affluence as physiologists
by building bigger garbage
cans.
REFERENCES
1. Adams, S. The MEDLARS System, Federation Proc. 22: 1018, 1963.
2, Cahn, J. Closing the Gaps in Biological
Communications.
Federation
Proc. 22: 993, 1963.
3. Communication
Problems in Biomedical
Research.
Natl. Acad. Sci.,
Natl, F&s. Council, Oct. 31, 1963. (Report of a Study).
4, Davis, H. The Physiologist.
1: 43, 1958.
THE PHYSIOLOGIST
342
Am. J. Physiol. 159: 551,
5. Fenn, W. 0. Physiology on Horseback.
1949.
History of the American
6. FeM, W. 0. The Third Quarter Century.
Physiological
Society. The American Physiological
Society, Washington, D.C., 1963.
for Science and Informa7. Kelsey, F. E. Government Responsibility
tion. Federation Proc. 22: 975, 1963.
Federation Proc. 22:
8. Price, D. Challenge to the Primary Journal.
1008, 1963.
9. Price, D. J. de Solla. Little Science. Big Science. Columbia Univ.
Press, New York, 1963.
and Information.
A Report of the President’s
10. Science, Government,
Advisory Committee.
The White House, Jan. 10, 1963.
11. Terry, L. Surgeon General’s Conference on Health Communications.
Nov. 5-8, Dept. HEW, 1962, p. 63.
M. B. Retrieval and Evaluation of Information.
The
12. Visscher,
Physiologist.
7: 29, 1964.
Federa13. Zwemer, R. Approaches to Keeping up with the Literature.
tion Proc. 22: 984, 1963.
FOR TRAVELERS
TO THE FAR EAST
The Department of Health Education and Welfare wishes to remind
travelers that the Division of Foreign Quarantine has issued two leaflets that are helpful to persons planning trips’ to the Western Pacific
and the Far East. One is entitled, “So You’re Going Abroad: Health
Hints for Travelers”
(PHS Publication
No. 748A); the other “Health
Information
for Travel in Asia (PHS Publication No. 748C). Each lists
the vaccinations
required and recommended
for travel in that part of
the world as well as health protection hints, such as what not to eat or
drink.
Copies can be obtained from the Superintendent
of Documents,
U. S. Government Printing Office, Washington,
D.C. 20402, for 5 cents
apiece.
AIBS
JOHN R. PAPPENHEIMER*
More than two years have elapsed since you have had a report from
your representative
to the American Institute of Biological
Sciences.
Most of you are aware that recent officers of the Institute inherited some
extremely complex administrative
and financial problems.
The financial
difficulties
arose mainly from mismanagement
of funds allocated by
the National Science Foundation for the production of the AIBS Educational Film Series prior to 1962. Little is to be gained by reviewing
the details of this mismanagement
except to emphasize that it involved
nothing which could be construed as dishonesty on the part of any individual.
Nevertheless it left AIBS in desperate financial difficulties
(see Science, 139:317-21,
1962) and seriously threatened the unity and
healthy development of biology in this country.
The new officers of
AIBS faced these problems intelligently
and courageously under the
leadership of Frits Went, President during 1962, James Ebert, President during 1963, Paul Kramer,
President during 1964, and John R.
Olive, the new Executive Director of the Institute.
AIBS has emerged
from its period of trial stronger,
wiser, and better equipped than previously to serve the needs of biological
sciences.
The lessons learned
were bitter ones and they are not likely to be lost upon the officers of
many scientific societies and universities
which accept funds from
government agencies.
Conversely,
the government granting agencies
also learned something from this experience which in the end helped to
clarify their function in supporting the biological
sciences.
All of us
owe a debt of gratitude to those who weathered the storm so resolutely.
Much remains to be done, but at this time we can say that AIBS
will enter 1965 with a balanced operational
budget, a practical long-term
schedule for payment of its debts and above all with the confidence and
enthusiasm of most of its members.
Before 1962 there were 27 societies
affiliated with AIBS; now there are no less than 43 adherent societies
representing
some 70,000 biologists.
At the same time, the number of
individual dues-paying members has increased to 12,000 and hopefully
this number will increase as the results of the AIBS programs come to
be more widely known and appreciated.
During this two-year period of administrative
stress, some of the
long-term
programs of AIBS came to fruition and it is now possible to
point to accomplishments
which can hardly fail to strengthen biology as
In recognition
of these accoma whole and physiology in particular.
plishments the Rockefeller Foundation has recently awarded $50,000 to
AIBS to aid in initiation of new programs.
Some of the solid accomplishments of AIBS may be summarized
as follows.
1. The Biological
Sciences Curriculum
Study Program.
Many of you
will have seen the new textbooks and laboratory manuals of biology
which are now being widely adopted in high schools throughout the
*APS Representative
to AIBS Board of Governors.
343
344
THE PHYSIOLOGIST
United States. The preparation
of these books through the cooperative
efforts of leading research biologists on the one hand and high school
teachers and students on the other, was a most interesting
experiment
initiated by AIBS five years ago. The final resu.lts based on three years
of practical experience in more than 1,000 high schools are now available in the form of bound volumes published on a large scale. Three
versions of the textbooks are available, the “Blue Version” (Molecules
to Man), the “Yellow Version”
(An Inquiry into Life) and the “Green
Version” (High School Biology).
The emphasis of each book is slightly
different as suggested by the titles, but each provides the basis for a
comprehensive
and thoroughly modern course in biology.
The presentation is challenging to the imagination
and often proceeds rapidly to
current problems.
A substantial fraction of the material is concerned
with the functional approach to the study of living things, including
general, systemic and mammalian physiology.
The balance between
Molecular
Biology, Biochemistry,
Cell Biology, Genetics, Microbiology,
Animal and Plant Physiology, Ecology, etc. seems very good and one
emerges from each book with a strong sense of the unity of biology as
a whole.
Each of the three books is supplemented by laboratory guides
and a program of films which were designed in conjunction with the
laboratory material and texts. Each film lasts about one-half hour and
there are 120 films covering 10 major subdivisions of biology.
The
effects of this enterprise
must surely be to revolutionize
the teaching
of biology in secondary schools and in colleges.
The implementation
of this new program in high schools throughout the country can be expected to capture new talent and to raise the caliber of the students whom
we shall see in graduate schools of Physiology and Medicine.
In the
words of James Ebert “‘there can be no doubt that the (BSCS-AIBS) program has brought new spirit and vitality, a new sense of urgency, to
biology teaching; the great wave of interest in teaching modern biology
spearheaded by BSCS is now overflowing into elementary and college
teaching ranks, engendering comprehensive
studies and constructive
criticism
by the schools themselves and by national commissions.”
The initiation of the program and the impetus for transforming
it
into reality came primarily
from AIBS and in my opinion this accomplishment alone merits our admiration
and firm support both as members of APS and as individual dues-paying members of AIBS.
2. Publications.
AIBS publishes two journals,
Bio Science and the
The quality of the first journal has imQuarterly Review of Biology.
proved enormously during the past two years, and there is every indication of further improvements
under the leadership of the new President of AIBS, Professor Kenneth Thimann of Harvard.
Bio Science is
published monthly; it describes the activities of AIBS and also contains
primary papers, original essays and reviews.
Special issues are devoted to particular
subjects in Biology such as Ecology, Marine Biology,
Biology of the Arctic, Etc. You will not receive this journal unless you
have joined AIBS as an individual member.
3. Symposia and Publications.
AIBS has sponsored and arranged more
than 25 symposia during the past two years.
The proceedings of these
symposia are usually published as books. Recent examples of special
THE PHYSIOLOGIST
345
interest to physiologists
include Marine Biology; Brain and Behaviour;
The X-Chromosome
of Man; Radiation Biology; Small Blood Vessel
Involvement in Diabetes Mellitus;
Fructose-l;
6-Diphosphate
and its
Role in Gluconeogenesis;
and Sharks and Survival.
AIBS has also
arranged for the translation
and publication of Russian monographs.
In addition to arranging for relatively small symposia and conferences,
the AIBS is gradually accumulating
experience in the management of
large international
congresses.
In 1969 it will undertake management
of the International
Congress of Botany which is at least as large as
our International
Congress of Physiology.
4. Annual Meetings of AIBS. For many of the 43 adherent societies,
the annual meeting of AIBS in August is the principle
scientific meeting
of the year. At the 1964 meetings in Boulder, Colorado there were
about 4500 registrants
and more than 1500 scheduled papers.
Twentyeight of the societies were represented
on the program and most of them
held their own business meetings and arranged banquets and social functions similar to those normally held by APS at its regular Fall meeting.
In addition, however, there were many cooperative and intersociety
programs.
Your representative
spent a most interesting
and enjoyable day
on Mt. Evans on a field trip symposium on Physiological
Ecology of
Alpine Environments
arranged jointly by the Division of Comparative
Physiology of the American Zoological Society and the Ecological Society
of America.
The responsibility
for arranging these large and invaluable annual
meetings is shouldered by the staff of AIBS and this is one of its continuing important functions.
PLANS FOR THE FUTURE
1. Administrative
Reorganization
of AIBS. The Constitution and Bylaws
of AIBS are still under study and a stable version may require some years
of further experience.
Two years ago the fundamental change to individual, rather than to Society membership,
was implemented.
Under this
system the adherent societies each pay relatively small annual dues.
For example, the annual dues of our Society are now $750 per year
(approximately
30 cents per member) instead of $2,000 prior to 1962.
The principal membership
income of AIBS is derived from individual
members who pay $10 each and who receive full voting and other privileges of AIBS, including subscription
to Bio Science. Each adherent
Society appoints one representative
to the Board of Governors of AIBS
for a four-year term.
In addition there are 12 representatives
to the
Board of Governors from members-at-large.
This Board, totalling
more than 55 members meets semi-annually
with the elected President
and other members of the Executive Council, to discuss and determine
policy and new programs.
2. The Future Home of AIBS. AIBS is about to move into new headquarters at 3900 Wisconsin Avenue, Washington, D. C. This move does
not provide for expansion, but rather consolidation
into a more pleasant
building with more economical and efficient use of floor space.
THE PHYSIOLOGIST
Consideration
is being given, however, to a permanent home for
AIBS in keeping with its national importance to biology.
It is entirely
possible that means will be found to consolidate with various “umbrella”
organizations
such as the Federation of American Societies for Experimental Biology and the Society for Experimental
Biology and Medicine.
In many areas the activities of these organizations
overlap and much
would be gained by improving communications
between them. This is
especially true in the fields of publication,
visiting scientist programs,
science communication
studies, symposium service facilities,
national
roster of personnel and placement services and other large scale national
and international
enterprises.
At the present time representatives
of
both AIBS and FASEB are exploring the possibility
of combining their
facilities to establish a national center to represent all of the biological
and medical sciences.
SUMMARY
AIBS has emerged from its administrative
and financial difficulties
greatly strengthened and better equipped than ever before to serve the
biological
sciences.
It now comprises 43 adherent societies representing 70,000 biologists.
There are 12,000 dues-paying individual members.
The Biological
Sciences Curriculum
Program,
initiated by AIBS
five years ago, has borne fruit with a series of integrated textbooks,
laboratory guides and films for comprehensive
and thoroughly modern
courses in Biology.
This program has been widely adopted in schools
throughout the country and is generally regarded as the most important
event in the history of biology teaching.
The program can hardly fail
to raise the number, caliber and level of training among students entering graduate schools of Physiology and Medicine.
AIBS has initiated or sponsored some 25 symposia during the past
two years.
It has published several excellent books of special interest
to physiologists.
It has also transformed
the AIBS Bulletin into a
monthly journal called Bio Science which is rapidly becoming as important as Science or Nature for the general biologist.
The annual meeting
of AIBS has become the principal meeting of many of the adherent societies.
The solid accomplishments
of AIBS merit our admiration
and support.
The Institute will enter 1965 with a balanced operational
budget but many
years may be required to repair the effects of mismanagement
in the
past. The chief source of income derives from the $10 annual dues of
individual m em be rs ,, As your representative
to AIBS I have studied its
programs and accomplishments
during the past two years and am convinced, as was my predecessor
Dr. Fenn, that the interests and work
of AIBS contribute to the goals and purposes of the American Physiological Society. I have no hesitation therefore in urging you to join AIBS
as individual members if you have not already done so.
COUNCILMANTOUR
ROBERT
E. FORSTER
Some Aspects of the Future of Physiology
A recurring
concern about the future of physiology is its relation
within a university to the clinical departments of the medical school on
the one hand and to the natural sciences and general biology departments
on the other, a gap which physiology is called upon to span in explaining
function in the higher animals. With biology becoming more “molecular”,
and with lessening interest in organ and system physiology,
this gap has
appeared to grow, and with it the problems of the physiologist
in performing his integrative
and pedagogic function.
One department with
interests in organ physiology may be considered too “clinical”,
and the
next with research intersts closer to the cellular level may be accused
of being too esoteric to be of help in preparing medical students for the
care of the sick. Some have suggested that physiology as a separate
discipline will disappear entirely,
its area of instruction
and research
being divided amongst biochemistry,
molecular biology and the several
clinical departments.
Another concern is the training of future physiologists.
In the face
of the enormous overload of pertinent information,
what should be taught?
Should the cellular,
biophysical and molecular biological material be
organized outside the physiology department?
How much physiology
should be taught medical students primarily
by clinical departments?
It occurred to Council that an excellent way to investigate the present
status of these problems and existing thoughts about their solution, would
be to visit several departments
of physiology in which new chairmen had
recently been appointed. These individuals
could be expected recently to
have given a great deal of thought, not only to the immediate present, but
to the future of physiology,
as the success of the department under their
leadership depends in no small way on its organization
and its teaching
functions.
They would also in general be of a newer generation of physiologists as compared to those guiding other departments.
This is a report of visits to departments of physiology in five medical
schools in the central and southern eastern seaboard and in the southwest.
These departments
were selected as noted above, because they had new
chairmen.
One chairman had been in office long enough to influence the
organization
of the department.
An effort was also made to visit departments with a wide geographic distribution,
and departments that had not
been visited by a President or Councilman recently.
Owing to the pecuniary structure of the tour and the large distances involved, these visits
were combined with other business and could not be made contiguously.
I was deeply impressed,
and grateful for the esteem in which the membership holds their Society, as demonstrated
by their efforts on my behalf
and the time they spent, usually at inconvenient hours, to inform me.
Innovations in the instruction
in physiology of two of the schools
visited were presented at the Teaching Session at the Federation ,Meetings
347
348
THE PHYSIOLOGIST
at Chicago in 1964.
As one could have predicted there were as many ways of handling
the teaching responsibilities
and intra-university
relationships
of a
department of physiology as there were departments
and universities
visited,
However the following changes were seen in more than one
department and might be considered as illustrative
of widespread
responses to currents of change.
1. Faced with the inexorable expansion of scientific information
within the finite limits of curricula,
there is a general tendency to decrease the number of topics covered in the medical school physiology
course, and to increase the detailed consideration
of the basic processes
and of areas in other sciences pertinent to each topic.
The subject
matter set aside is that which is less general in its usefulness,
that
retained provides a background for general medicine and surgery. In
other words the physiological
background for the lesser medical specialties is getting shorter and shorter shrift in the medical curricula.
One
form of curriculum
reorganization
is to provide a core course, made
up of the most fundamental and general topics, which is taken by all
students and at the same time offering instruction
in specialized
topics,
which may be elected, in such subjects as biophysics,
cellular physiology
and endocrinology.
This increased flexibility
is a small recompense
for the drastic choice forced on the physiology staff but does help the
graduate students and those medical students who are so prescient as
to know the medical specialty they will eventually elect.
2. The proportion
of teaching time devoted to laboratory experiments
over the past quarter of a century is now generally considered too large
and the number of experiments
has been decreased, with an increase in
the time given to conferences and small discussion groups.
It is felt
that the laboratory is not necessarily the most efficient mechanism for
teaching, that in fact it can get in the way, but that a balance between
the various methods of instruction
has to be sought.
3. A greater effort is being made to provide the students with the
opportunity to experience the satisfaction of a scholarly or experimental
investigation,
rather than to be told about it. These opportunities
range
from literary
research and presentation
before small groups on one
hand to guided laboratory investigation
on the other,, The object is not
to make investigators
out of each student, but to give them a feeling for
the research process.
4. Increasing assistance in the teaching of physiology is being obtained from members of clinical departments with special training in
These individuals may have joint appointments,
and in
physiology.
effect provide a larger faculty whose specialized
interests cover a wider
area. There is however an attendant danger that those less directly
associated with this teaching or in‘administrative
posts may conclude
that all of physiology can be taught by the staff of clinical departments.
It may be freely admitted that specialized
topics can be well taught by
clinicians interested in the pertinent medical specialty.
However
applied topics of physiology are supported by the basic physiology of
THE PHYSIOLOGIST
349
yesterday.
Individuals whose interests include the clinical care of
patients cannot keep up with advances in the more fundamental areas
as well as the professional
physiologist.
A clinician who teaches in
association with physiologists
has pertinent advances in distant fields
brought to his attention.
If he does not have this help, tomorrow will
find his teaching falling behind.
Turning over the responsibility
for
the teaching of physiology to a clinical department in a medical school
might produce short term organizational
savings, but would lead to
eventual bankruptcy.
5. The relationship
between a department of physiology in a medical
school and the rest of the university is becoming closer; some are becoming “university”
departments
in the true sense. While this has many
advantages and is symptomatic of a growing sense of unity in biology, it
does put increased stress on the physiology department in its relations
with the medical school and its clinical departments.
This shift in the
center of gravity towards the university biology department,
is necessary
in view of advances in cellular and molecular
physiology but can be expected to exacerbate the “hands versus brains” debate (E. G. Dimond,
Science, 142:445, 1963) that will always exist in medical schools and to
place the physiology department between the warring extremes.
CONCLUSION
The organization
of the curricula
of physiology appears to be undergoing changes, as indicated by a sampling of five departments,
that are
reasonable responses to the overwhelming
increase in the amount of information to be taught and to the exciting advances in molecular
and
Physiology is more of a bridge between basic biology
cellular biology.
and clinical medicine than some of her sister basic medical sciences
and is feeling the divergent pulls more acutely.
Knowledge of the function of living matter is still the ultimate goal which should not be lost
sight of along the way, This will certainly require the techniques and
disciplines
of the more rapidly expanding segments of biology.
To those physiologists
of faint heart, have faith. Consider “Biochemistry”
nee “Physiological
Chemistry. ” Certainly structure and
function has not been a major concern of this daughter science, where
the chemical reactions of individual molecules in solution have. In recent years it has become increasingly
necessary for the biochemist to
study the spatial organization
of reacting systems of molecules in order
to interpret
their importance in living cells, a pursuit which the unindoctrinated would have little difficulty discerning
as physiology.
NEWS
Ira A. Manville,
FROM
SENIOR
901 S. W. King Ave.,
MEMBERS
Portland,
Oregon
97205
I am on the Board of Governors of the Physicians and Surgeons
Hospital of this city. I am engaged in a two-year research program
for the Oregon-Washington-California
Pear Bureau trying to find new
nutritive and therapeutic uses for pears. With the practice I have
and the interests just mentioned,
I am very happy. I hope to do some
writing so that my work will not be entirely self-centered.
Bruno Kisch,
71 Maple St. , Brooklyn
25, N. Y.
I am still involved in research work in the field of electron microscopy of the heart, which in my age I would not like to interrupt for half
a year or a year. But I would gladly be available, if ever the possibility arises, to deliver a lecture or two somewhere on my special
working field, for instance the sarcosome theory of muscle function,
or on my latest discoveries
concerning the perinuclear
space as a
I am invited to give such a lecture
focus of high enzymatic activities.
in the fall at the meeting of Electron Microscopists
in Prague.
William
R Amberson,
Marine
Biological
Lab.,
Woods Hole,
Mass.
We have had an active and, I hope, successful experimental
program
here. The major advance has come through our 1960 discovery that
muscle enzymes unite with the fibrous proteins, in loose complexes
which are nevertheless
tight enough to detect and study in electrophoretic patterns.
Most recently we have been able to show that enzyme
activities in our type of press juice are much lower than those in homoThis observation demonstrates
that much
genates of the same muscles.
of the glycolytic series is bound to the ultrastructure
and is not free in
the sarcoplasmic
matrix,
as has been long believed.
H. B. Van Dyke, P. 0. Box 7432, Taipei, Taiwan (Dept. Pharmacology,
College of Physicians & Surgeons, 630 W. 168th St., New York 32, N.Y. )
I am in Taiwan for a year as Visiting Professor of Pharmacology
under the auspices of the China Medical Board of New York, Inc. My
principal assignment is in the National Defense Medical Center.
However I shall also have a close relationship
with the College of Medicine
of the National Taiwan University.
I expect to return to the United
States in the autumn of 1964.
H. S. Forbes, Association on American Indian Affairs, Inc., Committee
on Alaskan Policy (71 Forest St., Milton 86, Mass. )
I am spending full time working on committee of the AALA, particularly on Alaska problems.
At the request of the Eskimos and Indians
we try to help them carry out their own plans in adjusting to changing
*Supplied
by the APS Committee
350
for Senior Physiologists.
THE PHYSIOLOGIST
351
conditions.
It is intensely interesting
but not easy. Dr. Laurence
Irving at the University of Alaska is Director of the Zoophysiology
Department and is continuing his studies on adaptation to cold. Also
he has been a very helpful member of this committee.
A little native
paper which I helped to start is doing a valuable service of information
and communication,
and its circulation
is increasing.
If you know of
anyone who might be interested in seeing it, and even to subscribe,
please tell them to write to me.
Maurice
L. Tainter,
Sterling
Drug Company,
New York 18, N.Y.
I reach retirement
age next June but the company has asked me to
carry on for an indefinite period thereafter.
For the moment therefore
I am not considering
any alternative ways of occupying my time.
H. A. Abramson,
Editor, The Journal
Hosp., Amityville,
L. I., N. Y. )
of Asthma
Research
(South Oaks
The Journal would be glad to print papers dealing with any aspect
of lung and skin physiology and pathology.
We are also interested in
having papers dealing with immunological
mechanisms.
Stanley P. Heimann, Director
search (703 W. Phil-Ellena
Emeritus,
The Institute for Cancer HeSt., Mt. Airy, Philadelphia
19, Pa. )
My own retirement
has been pleasant even though I have no formal
classes to help teach. With Dr. Grace Medes I have just had a book
published by J. B. Lippincott Company on “Normal Growth and Cancer. ”
At the moment I am writing another.
These activities,
with letters to
colleagues in various parts of the world, have kept me comfortably
busy. I do, however, miss close contact with young people, a need
which I fulfill unofficially
in the Institute for Cancer Research of which
I was director for many years.
Lester IX. Dragstedt,
Florida,
Gainesville,
Research
Fla.
Professor
I am at present Research Professor
Florida,
so that, following my retirement
I found myself fully occupied in teaching
I was made very happy by receiving the
the American Medical Association,
for
practice.
Earl A. Hewitt, Iowa State University
reported that:
of Surgery,
University
of
of Surgery at the University of
from the University of Chicago,
and research.
This past June
Distinguished
Service Award of
research, teaching, and surgical
(Deceased Dec. 29, 1963) formerly
A Biomedical
Electronics
program at Iowa State University was initiated jointly in 1957 by the College of Engineering
and the College of
Veterinary
Medicine.
The Program is sponsored by the Departments
of Electrical
Engineering,
Veterinary
Anatomy, Veterinary
Physiology
and Pharmacology,
the Engineering
Experiment
Station and the Veterinary Medical Research Institute.
352
THE PHYSIOLOGIST
The primary purpose of the graduate program is the training of
engineering
graduate students in advanced methods of designing instruments for bio-medical
measurements,
in applying engineering
principles
and methods to the study of anatomy and physiology and of training graduate students in Veterinary
Medicine specializing
in advanced methods
of using modern instruments for solving medical research problems.
A Biomedical
Electronics
Laboratory
building has been erected
which contains an electronic shop, small animal quarters,
a fully
shielded and instrumented
surgery room, radiotracer
laboratories,
drug and chemical rooms and laboratory space. The program is supported by research and training grants.
E. Gellhorn,
2 Fellowship
Circle,
Santa Barbara,
Calif.
P. B. Hoeber (New York) published my book “Emotions and Emotional
in 1963.
Disord .ers” (in collaboration
with G. N. Loofbourrow)
I made a bequest to the University of Chicago for a prize in NeuroThe sum has been matched by contribution
of friends and
physiology.
The first E. Gellhorn Prize was awarded last June.
former students.
K. K. Chen, Dept. of Pharmacology,
Indianapolis
7, Ind.
Indiana University
I am thoroughly deli .ghted with my full time position
Campus.
of Pharmacology
on the Indianapolis
Franklin C. McLean,
37, Ill.
Dept. of Physiology,
Medical
Center,
in the department
Univ. of Chicago,
Chicago
All is well with me, and I am still on an NIH grant. A new book,
“Radiation,
Isotopes and Bone” by McLean and Budy, as one of a series
sponsored by AEC will be out before January 1, 1964.
Samuel E. Pond, Proj. Coordinator,
Rehabilitation
Research,
of Vocational Rehabilitation,
Hartford,
Conn. (53 Alexander
Manchester,
Conn. )
Bureau
St.,
I transferred
from laboratory work on brain-barrier
biochemistry
and college counseling to critical studies of administration
and operations in state-agency services which utilize expanding physical medicine
and psychiatry,
associated with educational guidance counseling to remotivate and re-direct
individuals with disabilities
which handicap them
in their professional,
semi-skilled
and even unskilled activities or employment.
A. E. Livingston,
120 W. Wayne Ave.,
Wayne Pa.
Having been head of Pharmacology
at Temple Medical from 1929
until their retirement
age, was made head of Pharmacology
at Temple
Pharmacy until retired at age 70 in 1954.
THE
353
PHYSIOLOGIST
St. John’s asked me to be head of their Pharmacy department of
Pharmacology
and after four years was made Coordinator
of Science
Laboratories
until retired, August 31, 1963.
J. F. McClendon,
R F. D. Route 1, Box 393, Norristown,
Pa.
I have been retired two years and have used the time writing a book
on the history of medicine from the physiologist’s
viewpoint with special
reference to new drugs obtained from Latin America.
Alex Forbes, The Biological
Ave., Cambridge,
Mass.
Laboratories,
Iam still doing resea rch.
retina of diurnal lizards.
Charles
H. Best,
Harvard
University,
Divinity
It is on the color s ense of the allcone
St. , Toronto,
112 College
Canada.
I am just going to chair a seminar by one of my pupils, D. G. Baker,
who has recently accepted a fine position as Senior Scientist at the Brookhaven National Laboratory.
Laurence Irving,
Alaska 99735.
Institute
of Arctic
Biology,
Univ.
of Alaska,
College,
A study of \some simple considerations
like age relations to research
and premature
cessation of research may show how scientific accomplishment can be increased without the new machinery and personnel that may
increase the overhead costs of science and introduce risk of diminishing
the effectiveness of the existing social scheme in which science operates.
Curt P. Richter, Phipps
Baltimore
5, Md.
Psychiatric
Clinic,
Johns Hopkins Hospital,
At the moment I am working full time at my old job - harder and
longer than before retirement
- and having a lot of fun. Hope, however,
to finish a monograph within the next few months based on last 8 years
work.
A.
Baird Hastings, Scripps
St., La Jolla, Calif.
I gave my first paper
the Baltimore meeting in
on the bicarbonate
content
have been: ‘The effect of
extracellular
fluid. “)
Clinic. and Research
Foundation,
476 Prospect
before the American Physiological
Society at
1919. It was entitled: “The effect of fatigue
of blood plasma. ” (Paraphrased,
this might
metabolism on the CO2 concentration
of an
My first paper before the Federation,
after my return to laboratory
work in 1959, was given at the 1962 meeting and the title was: “Effect
of CO2 concentration
on carbohydrate
metabolism in rat liver. ”
I have thus gone full circle
in 43 years - and find myself engaged in
354
THE PHYSIOLOGIST
one of the most interesting
problems
I’ve ever encountered.
H. E. Essex, President,
National
Bldg. , Mayo Clinic , Rochester,
Society for Medical
Minn. )
I have my hands full at present
for Medical Research.
with the affairs
Stuart Mudd,
Pa.
VA Hosp.,
University
& Woodland
Research
(Plummer
of the National
Aves.,
Society
Philadelphia
4,
I am greatly enjoying my Emeritus status, working half time as
Chief of the Microbiologic
Research Program at the U. S. Veterans
Administration
Hospital, Philadelphia.
This program is supported by
grants from the National Institutes of Health and the Veterans Administration Central Office Research Service.
Our program concerns
Pathogenesis, prevention and treatment of staphylococcal
infection.
In the other half of my time I have been much preoccupied
during the
past two and a half years with editing volume II of the World Academy of
Art and Science, “The Population Crisis and the Use of World Resources, ”
which should be published by Dr. W. Junk, of the Hague, next month. An
American edition will be published by the Indiana University Press in
April 19 64.
Roberta Hafkesbring,
Dept. of Physiology,
Pennsylvania,
East Falls, Philadelphia,
Woman’s
Pa.
Medical
College
of
Dr. Dong J. Kim, of Ewha University,
Seoul, Korea, has invited me
to teach for a year in the Medical School associated with that University.
I have promised to stay at Woman’s Medical College through the Spring
of 1964 and am planning to go to Korea during the Fall.
Arthur H. Steinhaus,
Chicago 15, Ill.
George Williams
College,
5315 Drexel
Ave.,
The year 1962-63 provided me with an interesting
opportunity to
serve in the Department of Physical Education of Tokyo University.
My assignment was to teach physiology as it applies to physical education, to graduate students.
Since my invitation was jointly from the
University of Tokyo and the Japanese Olympic Committee,
much of my
activity took place outside the University.
It was my privilege to lecture in some twenty-three
universities
and a large number of conferences. Outside of my regular assignment at the University I was permitted to make a total of 156 talks in the ten months.
Harry Goldblatt,
Ohio.
Mount Sinai Hospital,
University
Circle,
Cleveland
6,
Although I was obliged to retire from my position as Director of
Laboratories
of Mount Sinai Hospital, I was permitted to remain as the
Director of L. D. Beaumont Memorial
Research Laboratories
of this
institution,
and am gainfully employed.
THE PHYSIOLOGIST
355
F. D. W. Lukens, Cox Institute,
StS.,
Philadelphia
4, Pa.
University
Hospital,
36th & Spruce
I had the pleasure of working with Fred Hitchcock in Iran last year.
He was Visiting Professor of Physiology while I was Visiting Professor
of Medicine.
He is doing a fine job.
Edward 3. Van Liere, School of Medicine,
Morgantown,
W. Va.
Univ.
I still have two years at this University
ment is 70).
(mandatory
Our monograph,
Press is just out.
“Hypoxia”,
C. I. Heed, 1816 B. Riverside
published
Drive,
of West Virginia,
age of retire-
by the University
Columbus,
of Chicago
Ohio 43212
I’m trying to finish up a History of Physiology in North America
that has been brewing for twenty years. Part of it will be in the nature
of elaboration
of the installments
previously published in “The Physiologist. ‘1
Walter
C. Alvarez,
700 Michigan
Ave.,
Chicago,
Ill.
I am glad I had some seventeen years in physiology because I think
I am still thinking as a physiologist
in regard to many problems of
disease.
For years I could not make up my mind whether I should try
to stay in physiology which I loved, or to stay in clinical medicine,
which I also loved. Finally the depression of 1929 solved the problem
because I lost the appropriation
for my lab.
Anna Goldfeder, Cancer and Badiobiological
Research Laboratory,
York (99 Ft. Washington Ave., New York 32, N. Y.)
New
I have a civil service position with the Department of Hospitals,
City of New York, an associate professorship
at the New York University
and am in charge of this laboratory.
I am very pleased to say that I
have good facilities
to continue my research work here.
R G. Hoskins,
86 Varick
Hd., Waban 68, Mass.
I resigned my post as what amounted to the
of the Boston Branch Office of Naval Research
day 1963. My collaborators
at the office gave
going away party and subsequently,
a birthday
of the Secretary of the Navy presented me with
and commendatory
citation.
job of Medical Consultant
on my eighty-third
birthme a heart-warming
party at which the office
a very attractive plaque
Eleanor D. Mason, Dept. of Physiology,
Harvard
Health, 665 Huntington Ave., Boston 15, Mass.
From the Fall of 1964 I plan to go to England
School of Public
as one of a small
356
THE PHYSIOLOGIST
ecumenical community,
which we shall be starting there. One is a
doctor, one a nurse, and I a physiologist
- but we join as a religious
community.
We’ve all been in India. I expect we’ll all miss our professional lives - but are thankful for going where we can continue,
though older, to do, we hope, creative and useful work through prayer.
Oscar Riddle,
RF.D.
4, Plant City,
Fla.
In “The Third Quarter Century” (History of the American Physiological Society, 1937-1962) Dr. Fenn properly notes the important role
of the Society in the founding of both the Union of American Biological
Society and its successor,
the AIBS. It is little recognized,
but here
notable, that the Union - through sponsorship of a self-sustaining
of the National Association of
committee - became the foster-parent
Biology Teachers,
now apparently the largest (over 8,000 members)
of our independent biological
societies.
G. H. Wang, 283 Medical
Wis. 53706.
Science Bldg.,
Univ.
of Wisconsin,
Madison,
‘The University of Wisconsin Press will publish in April 1964 G. H.
Wang’s “The Neural Control of Sweating. ” This monograph summarized
the work of Wang and his associates up to July 1962 on the control mechanisms of the neural control of sweat secretion in anesthetized and nonanesthetized cats. ”
El *even “over-eighty-five”
some of them were adolescing
W.
C.
P.
E.
T.
P.
A.
E.
0.
T.
G.
members were heard from. We note that
when our Society was founded in 1887.
H. Lewis:
No comment.
D. Snyder: “In good health”.
M. Dawson: “Thanks”
L. Opie: “Thank you for the opportunities
suggested. ”
Sollman: “I am 89. ”
B. Hawk: “I have retired. ”
“If I should say ‘Yes’ to any of these questions,
N. Richards:
you would say ‘No’ - and you would be right. ”
L. Scott: “No outside activities. ”
Riddle: “Most answers must be ‘No’. (Also see news item).
S. Githens: ” I am over 85 years old. ”
H. Whipple:
“No plans to leave Rochester. ”